Interleukin-32-induced thymic stromal lymphopoietin plays a critical role in macrophage differentiation through the activation of caspase-1 in vitro
- Hyun-Ja Jeong†1,
- Sun-Young Nam†2,
- Hyun-A Oh2,
- Na-Ra Han2,
- Young-Sick Kim2,
- Phil-Dong Moon2Email author,
- Seung-Youp Shin3,
- Min-Ho Kim4 and
- Hyung-Min Kim2Email author
© Jeong et al.; licensee BioMed Central Ltd. 2012
Received: 11 July 2012
Accepted: 27 November 2012
Published: 28 November 2012
Interleukin (IL)-32 is an inflammatory cytokine induced by Mycobacterium tuberculosis and Mycobacterium bovis in a variety of cell types and discovered in the synovial of patients with rheumatoid arthritis (RA). Thymic stromal lymphopoietin (TSLP) play several roles in the pathogenesis of RA. However, the role of IL-32 and TSLP in RA has not been elucidated.
We evaluated the specific mechanism of between IL-32 and TSLP in RA using human monocyte cell line, THP-1 cells.
Here we documented for the first time that IL-32 highly increased TSLP production in THP-1 cells and human blood monocytes. TSLP expression was induced by IL-32 via activation of caspase-1 and nuclear factor-κB. TSLP produced by IL-32 increased differentiation of monocytes but depletion of TSLP prevented differentiation of monocytes into macrophage-like cells. Chondroprotective drugs such as chondroitin sulfate (CS) and the traditional Korean medicine, BaekJeol-Tang (BT) decrease production of TSLP and activation of caspase-1 and nuclear factor-κB. In addition, CS and BT inhibited IL-32-induced monocytes differentiation.
Taken together, IL-32 and TSLP are important cytokines involved in the development of RA. The effects of CS and BT were associated with the downregulation of TSLP and caspase-1 through negative regulation of IL-32 pathways in RA.
Rheumatoid arthritis (RA) is characterized by a chronic inflammation of synovial joints that leads to a progressive destruction of articular and periarticular structures, causing severe morbidity and disability . In RA, the extensive infiltration of inflammatory cells into the synovium and the tumor-like proliferation of RA synovial fibroblasts (RASF) cause the formation of a hyperplastic pannus, which aggressively invades and destroys underlying cartilage and bone. Until now, the role of macrophages, T and B cells, neutrophils, and RASF in the pathophysiology of RA have been examined extensively [2–6].
Interleukin (IL)-32 is a recently described cytokine produced by T lymphocytes, natural killer cells, epithelial cells, mast cells, keratinocytes, eosinophils, and blood monocytes [7–11] and was discovered in the synovial of patients with rheumatoid arthritis but not osteoarthritis . IL-32 was induced by Mycobacterium tuberculosis and Mycobacterium bovis bacillus Calmette-Guérin as well as by either lipopolysaccharide (LPS) or mycobacteria . Moreover, IL-32 production induced by M. tuberculosis is dependent on endogenous interferon-γ (IFN-γ) . A recent study demonstrated that overexpression of the inflammatory mediator, cyclooxygenase 2 resulted in increased IL-32 levels . IL-32 induces the production of tumor necrosis factor (TNF)-α, IL-1β, IL-6, and IL-8 by means of the activation of nuclear factor (NF)-κB, p38 mitogen-activated protein kinase (MAPK), and caspase-1 [7, 8, 11]. IL-32 also modulates the signals induced by specific Toll-like receptors (TLRs) and nucleotide oligomerization domain (NOD) ligands. IL-32 synergized with NOD1 and NOD2 ligands for the synthesis of IL-1β and IL-6 via activation of caspase-1 .
Thymic stromal lymphopoietin (TSLP) is associated with RA, allergic rhinitis and atopic dermatitis [15–17]. It might initiate T helper cell type 2 (Th2) polarization through an OX40-dependent mechanism that affects dendritic cells (DC) activity [17, 18]. Signaling of cells by TSLP requires IL-7 receptor . and a distinctive receptor subunit, the TSLP receptor (TSLPR), which is expressed by myeloid DC, monocytes, preactivated T cells, natural killer cells, and mast cells [18, 20–22]. In humans, TSLP potently stimulates myeloid DC, with upregulated expression of CD40, CD80, CD86, OX40L, and CD83 and production of chemokines, including thymus and activation-regulated chemokine and macrophage-derived chemokine [23, 24]. TSLP was expressed by TNF-α and IL-1β in human airway smooth muscle cells via MAPK, p38 and extracellular signal-regulated kinase (ERK) signaling pathway . Recently, we reported that TSLP was expressed and produced by caspase-1 and NF-κB activation in mast cells .
Although the above-mentioned findings indicate a likely role of IL-32 and TSLP in RA, the specific mechanism of between IL-32 and TSLP have not previously been studied. In this study, we report that IL-32 induces TSLP production and monocyte-to-macrophage differentiation through caspase-1. We also investigated the effect of useful therapeutic agents in RA, chondroitin sulfate (CS) and the traditional Korean medicine, BaekJeol-Tang (BT), in IL-32-induced TSLP production and monocyte differentiation.
Materials and methods
We purchased 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), bicinchoninic acid, caspase-1 inhibitor (CI), pyrrolidine dithiocarbamate (PDTC), lipopolysaccharide (LPS), dimethyl sulfoxide (DMSO), CS, and caspase-1 inhibitor from Sigma-Aldrich (St. Louis, MO, USA); recombinant IL-32, recombinant TSLP, caspase-1 assay kit, and recombinant caspase-1 from R&D Systems (Minneapolis, MN, USA); NF-κB, actin, histone, and caspase-1 antibodies from Santa Cruz Biotechnology (Santa Cruz, CA, USA); CD11b and CD14 antibodies from eBioscience (San Diego, CA, USA); TSLP SMART pool from Dharmacon Inc. (Chicago, IL, USA).
Preparation of BT and CS
BT is composed of shark cartilage (24 g), Atractylodis Rhizoma (Atractylodes lancea De Candolle, 8 g), Phellodendri Cortex (Phellodendron amurense Ruprecht, 8 g), and Sophora Radix (Sophora flavescens Solander ex Aiton, 8 g). BT (voucher number 201101) was obtained from TeunTeunMaDi Korean Medical Clinic (Seoul, Republic of Korea) and identified by Dr Hyung-Min Kim of the College of Oriental Medicine, Kyung Hee University. An extract of BT was prepared by decocting the dried prescription of herbs with boiling distilled water (48 g/l). The product was filtered, lyophilized and kept at 4°C. The yield of dried product from starting materials was about 35.6%. CS is a major component of shark cartilage. The samples were dissolved in distilled water and then filtered through a 0.22 μm syringe filter.
Human monocyte cell line, THP-1 was obtained from the American Type Culture Collection (TIB-202; Manassas, VA, USA). THP-1 cells were cultured in RPMI 1640 supplemented with 10% fetal bovine serum (FBS) and 2 mM glutamine and were maintained at a concentration between 2 and 10 × 105 cells per milliliter.
Isolation of peripheral blood mononuclear cells (PBMCs)
PBMCs were isolated from healthy human volunteers. The donors were free of prescribed and over-the-counter medications. After informed consent, PBMCs from heparinized venous blood were isolated with Ficoll gradient centrifugation according to the manufacturer's specification (Sigma-Aldrich, MO, USA). This study was approved by the local ethics committee of Kyung Hee University Hospital in Seoul, Republic of Korea (KMC IRB 1222-06)
THP-1 cells were treated with various concentrations of IL-32 for 24 h. The production of TSLP was measured from cells culture supernatant according to the manufacturer's specifications (R&D Systems, Minneapolis, MN, USA).
Reverse transcription PCR analysis
Using an easy-BLUE™ RNA extraction kit (iNtRON Biotechnology, Republic of Korea), we isolated the total RNA from THP-1 cells in accordance with the manufacturer's specification. The concentrations of total RNA in the final elutes were determined by spectrophotometer. Total RNA (1 mg) was heated at 65°C for 10 min and then chilled on ice. Each sample was reverse-transcribed to cDNA for 90 min at 37°C using a cDNA synthesis kit (Amersham Pharmacia Biotech, Piscataway, NJ, USA). The PCR was performed with the following primer for human TSLP (5' TAT GAG TGG GAC CAA AAG TAC CG 3'; 5' GGG ATT GAA GGT TAG GCT CTG G 3') and GAPDH (5'CAA AAG GGT CAT CAT CTC TG 3'; 5'CCT GCT TCA CCA CCT TCT TG 3'). The annealing temperature was 62°C for TSLP and GAPDH. Products were electrophoresed on a 2% agarose gel and visualized by staining with ethidium bromide.
Quantitative real-time PCR analysis
Quantitative real-time PCR was performed using a SYBR Green Master Mix and the detection of mRNA was analyzed using an ABI StepOne Real-Time PCR System (Applied Biosystems, Foster City, CA, USA). Primer sequences for the reference gene GAPDH and the genes of interest were as follows: GAPDH (5'TCG ACA GTC AGC CGC ATC TTC TTT 3'; 5'ACC AAA TCC GTT GAC TCC GAC CTT 3'); human TSLP (5 CCC AGG CTA TTC GGA AAC TCA G 3'; 5' CGC CAC AAT CCT TGT AAT TGT G 3'); human CD11b (5'ACG TAA ATG GGA CAA GCT G 3'; 5'GAT CCT GAG GTT CCG TGA AA 3'); human CD14 (5'ACT TGC ACT TTC CAG CTT GC 3'; 5'GCC CAG TCC AGG ATT GTC AG 3'). Typical profile times used were the initial step, 95°C for 10 min followed by a second step at 95°C for 15 s and 60°C for 30 s for 40 cycles with a melting curve analysis. The level of target mRNA was normalized to the level of the GAPDH and compared with the control. Data were analyzed using the ΔΔCT method.
Caspase-1 enzymatic activity assay
Caspase-1 enzymatic activity was measured according to the manufacturer's specification by using a caspase assay kit.
Western blot analysis
The stimulated cells were lysed and separated through 10% SDS-PAGE. After electrophoresis, the protein was transferred to nitrocellulose membranes and then the membranes were blocked and incubated with primary and secondary antibodies. Finally, the protein bands were visualized by an enhanced chemiluminesence assay purchased from Amersham Co. (Newark, NJ, USA) following the manufacturer's instructions.
Transient transfection and luciferase assay
For the transfection, we seeded THP-1 cells (1 × 107) in a 100 mm culture dish. We then used Lipofectamine™ 2000 purchased from Invitrogen (Carlsbad, CA, USA) to transiently transfect pNF-κB luciferase (LUC) and pSV40-LUC reporter gene constructs into THP-1 cells. To measure the luciferase activity, we used a luminometer 1420 luminescence counter purchased from Perkin Elmer (Waltham, MA, USA) in accordance with the manufacturer's protocol. All the transfection experiments were performed in at least three different experiments, with similar results. The relative luciferase activity was defined as the ratio of firefly luciferase activity to renilla luciferase activity.
Analysis of monocyte surface antigens by flow cytometry and confocal laser scanning microscopy
THP-1 cultured in the presence or absence of IL-32, TSLP, CI, CS, and BT for 6 days were washed in fluorescence-activated cell sorter (FACS) buffer (phosphate-buffered saline supplemented with 1% bovine serum albumin and 0.1% NaN) and then incubated with 2 μl of fluorescein isothiocyanate (FITC)-conjugated CD14 and phycoerythrin (PE)-conjugated CD11b antibodies for 30 min at 4°C. After washing with FACS buffer, cells were fixed with 1% (weight/volume) paraformaldehyde for 30 min and then stored in the dark until analyzed by flow cytometry. Cytofluorometry was performed with a FACScan (Becton Dickinson, Mountain View, CA, USA). All specimens were examined with a confocal laser scanning microscope.
All results are expressed as the mean ± SEM. The statistical evaluation of the results was performed by an independent t test and an ANOVA with a Tukey post hoc test. The results are significant with a value of P < 0.05.
Upregulation of TSLP production and mRNA expression in IL-32-treated THP-1 cells
Caspase-1 and NF-κB involvement in IL-32-induced TSLP production and mRNA expression
Role of caspase-1 in IL-32-induced macrophage-like cells differentiation
Role of TSLP in IL-32-induced macrophage-like cells differentiation
Effect of BT and CS on IL-32 or LPS-induced TSLP production and mRNA expression
Effect of BT and CS in IL-32 or LPS-induced caspase-1 and NF-κB activation
We investigated whether BT and CS would influence the activation of caspase-1 induced by IL-32 or LPS in THP-1 cells. Western blot analysis for caspase-1 was performed. Caspase-1 activation by IL-32 or LPS was decreased by the treatment of BT or CS (Figure 5E and 5F). We also estimated the effect of BT and CS on caspase-1 activation using a caspase-1 assay kit. Once again, this showed that caspase-1 activity was significantly inhibited by the treatment of BT or CS (Figure 5G and 5H, P < 0.05). The expression of TSLP mRNA was regulated by the transcription factor, NF-κB . Because the suppression of NF-κB is linked with anti-inflammation, we postulated that BT and CS mediate its effects at least partly through the suppression of NF-κB activation. To assess the regulatory mechanism of BT and CS on TSLP mRNA expression, we examined the regulatory effect of BT and CS on the translocation of NF-κB into the nucleus. The stimulation with IL-32 or LPS increased translocated levels of NF-κB in the nucleus but the translocated levels of NF-κB were suppressed by the treatment of BT or CS (Figure 5E and 5F).
Effect of BT and CS in IL-32-induced macrophage-like cells differentiation
In the present study, we demonstrated that IL-32 induced the TSLP production and mRNA expression via activation of caspase-1 and NF-κB. IL-32 and TSLP also increased the differentiation of THP-1 cells. In addition, CS and BT inhibited the differentiation of THP-1 cells through inhibition of TSLP production and caspase-1 activation.
IL-32 plays an important role in host defense against microorganisms including Mycobacterium, HIV, and influenza [13, 29–31]. IL-32 has also been implicated in several inflammatory disorders, including rheumatoid arthritis, Crohn's disease, atopic dermatitis, chronic obstructive pulmonary disease, and allergic rhinitis [9, 11, 12, 32, 33]. IL-32 expression is related with disease severity in these conditions. Recently, we have been shown that silencing of endogenous IL-32 results in the reduction of IL-6, IL-8, TNF-α, and vascular endothelial growth factor (VEGF) . TSLP produced the IL-5, IL-6, IL-13, and granulocyte macrophage colony-stimulating factor from mast cells . TSLP expression correlates with markers of inflammation. TSLP-induced immune activation increased the joint destruction, because TSLPR-/-mice displayed decreased cartilage and bone erosion, decreased number of tartrate-resistant acid phophatase-positive osteoclasts, and reduced local expression of factors that are involved in tissue destruction . Block of TSLP reduced the severity of collagen-induced arthritis . From this, we can presuppose that TSLP produced by IL-32 plays an important role in expression of inflammatory cytokines. These properties suggest that IL-32-induced TSLP might play an important role in the amplification of inflammatory reactions such as RA. Future studies will be required to investigate whether TSLP acts as an endogenous regulator of proinflammatory cytokine production in monocytes.
It has been shown that IL-32 potentiates one or more of the intracellular pathways induced by NOD ligands. Synthetic muramyl dipeptide engagement of NOD2 results in the activation of two signaling pathways. First, NOD2 activates the serine/threonine kinase receptor-interacting protein 2/RICK/CARDIAK, and this leads to NF-κB activation and transcription of proinflammatory cytokine genes such as those encoding TNF-α, IL-1β, and IL-6 . Second, the CARD domain of NOD-like receptors proteins interacts with caspase-1 and 5, and this interaction results in the processing of cytokine precursors such as pro-IL-1β and pro-IL-18 . In this study, IL-32 increased the caspase-1 and NF-κB activation in THP-1 cells. Caspase-1 inhibitor or NF-κB inhibitor reduced the IL-32-induced TSLP production and mRNA expression. Taken together, these reports imply that IL-32 induces TSLP production and mRNA expression in THP-1 cells through a signaling cascade downstream of the caspase-1 and NF-κB activation.
Both the innate and acquired immune systems rely heavily upon the effector and regulatory activities of monocytes and macrophages . Differentiation of myeloid cells involves broad-based and tightly regulated changes in gene expression induced in response to diverse cytokines, growth factors and other agonists [36, 37]. Expression of CD11b and CD14 is upregulated during myeloid cell differentiation. Myeloid zinc finger-1 is involved downstream of phosphatidylinositide 3-kinase in a calcitriol-induced signaling pathway leading to myeloid cell differentiation and activation of CD11b and CD14 . Recent studies by Netea and colleagues reported that IL-32 induced a consistent increase in the expression of both CD1a and CD14 . TSLP is capable of activating dendritic cells to promote Th2 immune responses. TSLP has also been shown to directly promote Th2 differentiation of naïve CD4 (+) T cell and activate natural killer T cells, basophils and other innate immune cells at the initial stage of inflammation . We also observed that IL-32 induces differentiation of THP-1 cells into macrophage-like cell. Netea et al., showed caspase-3 activation, but not caspae-1, -8, -9, plays an important role in monocyte differentiation . However, we investigated that caspase-1 inhibitor reduced the CD11b and CD14 expression through the inhibition of TSLP production. We also showed that TSLP siRNA inhibited the monocyte differentiation. For that reason, we suggest that blockade of IL-32 and TSLP signaling may be effective in prevention and treatment in models of inflammatory arthritis.
The suppressing of TSLP production signaling in THP-1 cells may be a useful tool to reduce monocyte differentiation in inflammatory conditions. CS belongs to the class of natural complex polysaccharides and is an unbranched, polydisperse, complex macromolecule extracted and purified from various tissues . It is a useful therapeutic agent in diseases such as inflammatory bowel diseases, artherosclerosis, Parkinson's and Alzheimer's diseases, multiple sclerosis, amyotrophic lateral sclerosis, rheumatoid arthritis, and systemic lupus erythematosus . CS diminishes the expression of inflammatory proteins via inhibiting of NF-κB nuclear translocation in chondrocyte, synovial macrophages, synoviocytes, and peripheral blood mononuclear cells . In previous studies, David-Raoudi et al., reported that CS increases hyaluronan production through upregulation of the expression of hyaluronan synthases . BT, a traditional Korean medicine, has long been prescribed as a treatment for joint diseases to protect injured chondrocytes. However, effect of these drugs has not been elucidated on TSLP production and monocyte differentiation. In this study, we showed that BT or CS significantly inhibited the production of TSLP, activation of caspase-1 and NF-κB, and differentiation of monocytes in THP-1 cells. Therefore, our finding provides new evidence that chondroprotective effect caused by the treatment of BT and CS is related to the inhibition of TSLP production and monocyte differentiation.
In conclusion, we show for the first time that IL-32 induces TSLP production by increasing NF-κB and caspase-1 activation. IL-32-induced TSLP induces differentiation of monocytes into macrophage-like cells with characteristic surface markers (CD11b and CD14). To our knowledge, this is also the first study to demonstrate that chondroprotective effect of BT and CS is accompanied by a regulation of TSLP production. Our results have demonstrated an essential role for the IL-32/TSLP pathway in RA. Further investigation is necessary to determine other possible mechanisms of IL-32 and TSLP and to apply it clinically in RA and other inflammatory diseases.
extracellular signal-regulated kinase
fluorescence-activated cell sorter
fetal bovine serum
mitogen-activated protein kinase
nucleotide oligomerization domain
peripheral blood mononuclear cells
reverse transcriptase time polymerase chain reaction
small interfering RNA
tumor necrosis factor
thymic stromal lymphopoietin
This work was supported by Kyung Hee University (KHU-20110092). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
- Feldmann M, Brennan FM, Maini RN: Rheumatoid arthritis. Cell. 1996, 85: 307-310. 10.1016/S0092-8674(00)81109-5.View ArticlePubMedGoogle Scholar
- Kinne RW, Brauer R, Stuhlmüller B, Palombo-Kinne E, Burmester GR: Macrophages in rheumatoid arthritis. Arthritis Res. 2000, 2: 189-202. 10.1186/ar86.PubMed CentralView ArticlePubMedGoogle Scholar
- Huber LC, Distler O, Tarner I, Gay RE, Gay S, Pap T: Synovial fibroblasts: key players in rheumatoid arthritis. Rheumatology (Oxford). 2006, 45: 669-675. 10.1093/rheumatology/kel065.View ArticleGoogle Scholar
- Firestein GS, Zvaifler NJ: How important are T cells in chronic rheumatoid synovitis? II. T cell-independent mechanisms from beginning to end. Arthritis Rheum. 2002, 46: 298-308. 10.1002/art.502.View ArticlePubMedGoogle Scholar
- Kasama T, Miwa Y, Isozaki T, Odai T, Adachi M, Kunkel SL: Neutrophil-derived cytokines: potential therapeutic targets in inflammation. Curr Drug Targets Inflamm Allergy. 2005, 4: 273-279. 10.2174/1568010054022114.View ArticlePubMedGoogle Scholar
- Martinez-Gamboa L, Brezinschek HP, Burmester GR, Dorner T: Immunopathologic role of B lymphocytes in rheumatoid arthritis: rationale of B cell-directed therapy. Autoimmun Rev. 2006, 5: 437-442. 10.1016/j.autrev.2006.02.004.View ArticlePubMedGoogle Scholar
- Kim SH, Han SY, Azam T, Yoon DY, Dinarello CA: Interleukin-32: a cytokine and inducer of TNF alpha. Immunity. 2005, 22: 131-142.PubMedGoogle Scholar
- Netea MG, Azam T, Ferwerda G, Girardin SE, Walsh M, Park JS, Abraham E, Kim JM, Yoon DY, Dinarello CA, Kim SH: IL-32 synergizes with nucleotide oligomerization domain (NOD) 1 and NOD2 ligands for IL-1beta and IL-6 production through a caspase 1-dependent mechanism. Proc Natl Acad Sci USA. 2005, 102: 16309-16314. 10.1073/pnas.0508237102.PubMed CentralView ArticlePubMedGoogle Scholar
- Meyer N, Zimmermann M, Bürgler S, Bassin C, Woehrl S, Moritz K, Rhyner C, Indermitte P, Schmid-Grendelmeier P, Akdis M, Menz G, Akdis CA: IL-32 is expressed by human primary keratinocytes and modulates keratinocyte apoptosis in atopic dermatitis. J Allergy Clin Immunol. 2010, 125: 858-865. 10.1016/j.jaci.2010.01.016.View ArticlePubMedGoogle Scholar
- Kempuraj D, Conti P, Vasiadi M, Alysandratos KD, Tagen M, Kalogeromitros D, Kourelis T, Gregoriou S, Makris M, Stavrianeas NG, Theoharides TC: IL-32 is increased along with tryptase in lesional psoriatic skin and is up-regulated by substance P in human mast cells. Eur J Dermatol. 2010, 20: 865-867.PubMed CentralPubMedGoogle Scholar
- Jeong HJ, Shin SY, Oh HA, Kim MH, Cho JS, Kim HM: IL-32 up-regulation is associated with inflammatory cytokine production in allergic rhinitis. J Pathol. 2011, 224: 553-563. 10.1002/path.2899.View ArticlePubMedGoogle Scholar
- Joosten LA, Netea MG, Kim SH, Yoon DY, Oppers-Walgreen B, Radstake TR, Barrera P, van de Loo FA, Dinarello CA, van den Berg WB: IL-32, a proinflammatory cytokine in rheumatoid arthritis. Proc Natl Acad Sci USA. 2006, 103: 3298-3303. 10.1073/pnas.0511233103.PubMed CentralView ArticlePubMedGoogle Scholar
- Netea MG, Azam T, Lewis EC, Joosten LA, Wang M, Langenberg D, Meng X, Chan ED, Yoon DY, Ottenhoff T, Kim SH, Dinarello CA: Mycobacterium tuberculosis induces interleukin-32 production through a caspase-18/interferon-gamma-dependent mechanism. PLoS Med. 2006, 3: e277-10.1371/journal.pmed.0030277.PubMed CentralView ArticlePubMedGoogle Scholar
- Lee S, Kim JH, Kim H, Kang JW, Kim SH, Yang Y, Kim J, Park J, Park S, Hong J, Yoon DY: Activation of the interleukin-32 pro-inflammatory pathway in response to human papillomavirus infection and over-expressionof interleukin-32 controls the expression of the humanpapillomavirus oncogene. Immunology. 2011, 132: 410-420. 10.1111/j.1365-2567.2010.03377.x.PubMed CentralView ArticlePubMedGoogle Scholar
- Hartgring SA, Willis CR, Dean CE, Broere F, van Eden W, Bijlsma JW, Lafeber FP, van Roon JA: Critical proinflammatory role of thymic stromal lymphopoietin and its receptor in experimental autoimmune arthritis. Arthritis Rheum. 2011, 63: 1878-1887. 10.1002/art.30336.View ArticlePubMedGoogle Scholar
- Bunyavanich S, Melen E, Wilk JB, Granada M, Soto-Quiros ME, Avila L, Lasky-Su J, Hunninghake GM, Wickman M, Pershagen G, O'Connor GT, Weiss ST, Celedón JC: Thymic stromal lymphopoietin (TSLP) is associated with allergic rhinitis in children with asthma. Clin Mol Allergy. 2011, 9: e1-10.1186/1476-7961-9-1.View ArticleGoogle Scholar
- Ziegler SF, Artis D: Sensing the outside world: TSLP regulates barrier immunity. Nat Immunol. 2010, 11: 289-293. 10.1038/ni.1852.PubMed CentralView ArticlePubMedGoogle Scholar
- Allakhverdi Z, Comeau MR, Jessup HK, Yoon BR, Brewer A, Chartier S, Paquette N, Ziegler SF, Sarfati M, Delespesse G: Thymic stromal lymphopoietin is released by human epithelial cells in response to microbes, trauma, or inflammation and potently activates mast cells. J Exp Med. 2007, 204: 253-258. 10.1084/jem.20062211.PubMed CentralView ArticlePubMedGoogle Scholar
- Park LS, Martin U, Garka K, Gliniak B, Di Santo JP, Muller W, Largaespada DA, Copeland NG, Jenkins NA, Farr AG, Ziegler SF, Morrissey PJ, Paxton R, Sims JE: Cloning of the murine thymic stromal lymphopoietin (TSLP) receptor: formation of a functional heteromeric complex requires interleukin 7 receptor. J Exp Med. 2000, 192: 659-670. 10.1084/jem.192.5.659.PubMed CentralView ArticlePubMedGoogle Scholar
- Reche PA, Soumelis V, Gorman DM, Clifford T, Liu Mr, Travis M, Zurawski SM, Johnston J, Liu YJ, Spits H, de Waal Malefyt R, Kastelein RA, Bazan JF: Human thymic stromal lymphopoietin preferentially stimulates myeloid cells. J Immunol. 2001, 167: 336-343.View ArticlePubMedGoogle Scholar
- Rochman I, Watanabe N, Arima K, Liu YJ, Leonard WJ: Cutting edge: direct action of thymic stromal lymphopoietin on activated human CD4 T cells. J Immunol. 2007, 178: 6720-6724.View ArticlePubMedGoogle Scholar
- Nagata Y, Kamijuku H, Taniguchi M, Ziegler S, Seino K: Differential role of thymic stromal lymphopoietin in the induction of airway hyperreactivity and Th2 immune response in antigen-induced asthma with respect to natural killer T cell function. Int Arch Allergy Immunol. 2007, 144: 305-314. 10.1159/000106319.View ArticlePubMedGoogle Scholar
- Watanabe N, Hanabuchi S, Soumelis V, Yuan W, Ho S, de Waal Malefyt R, Liu YJ: Human thymic stromal lymphopoietin promotes dendritic cell-mediated CD4 T cell homeostatic expansion. Nat Immunol. 2004, 5: 426-434. 10.1038/ni1048.View ArticlePubMedGoogle Scholar
- Liu YJ: TSLP in epithelial cell and dendritic cell cross talk. Adv Immunol. 2009, 101: 1-25.PubMed CentralView ArticlePubMedGoogle Scholar
- Zhang K, Shan L, Rahman MS, Unruh H, Halayko AJ, Gounni AS: Constitutive and inducible thymic stromal lymphopoietin expression in human airway smooth muscle cells: role in chronic obstructive pulmonary disease. Am J Physiol Lung Cell Mol Physiol. 2007, 293: L375-382. 10.1152/ajplung.00045.2007.View ArticlePubMedGoogle Scholar
- Moon PD, Kim HM: Thymic stromal lymphopoietin is expressed and produced by caspase-1/NF-κB pathway in mast cells. Cytokine. 2011, 54: 239-243. 10.1016/j.cyto.2011.03.007.View ArticlePubMedGoogle Scholar
- Netea MG, Lewis EC, Azam T, Joosten LA, Jaekal J, Bae SY, Dinarello CA, Kim SH: Interleukin-32 induces the differentiation of monocytes into macrophage-like cells. Proc Natl Acad Sci USA. 2008, 105: 3515-3520. 10.1073/pnas.0712381105.PubMed CentralView ArticlePubMedGoogle Scholar
- He R, Geha RS: Thymic stromal lymphopoietin. Ann NY Acad Sci. 2010, 1183: 13-24. 10.1111/j.1749-6632.2009.05128.x.PubMed CentralView ArticlePubMedGoogle Scholar
- Bai X, Kim SH, Azam T, McGibney MT, Huang H, Dinarello CA, Chan ED: IL-32 is a host protective cytokine against Mycobacterium tuberculosis in differentiated THP-1 human macrophages. J Immunol. 2010, 184: 3830-3840. 10.4049/jimmunol.0901913.View ArticlePubMedGoogle Scholar
- Nold MF, Nold-Petry CA, Pott GB, Zepp JA, Saavedra MT, Kim SH, Dinarello CA: Endogenous IL-32 controls cytokine and HIV-1 production. J Immunol. 2008, 181: 557-565.View ArticlePubMedGoogle Scholar
- Li W, Sun W, Liu L, Yang F, Li Y, Chen Y, Fang J, Zhang W, Wu J, Zhu Y: IL-32: a host proinflammatory factor against influenza viral replication is upregulated by aberrant epigenetic modifications during influenza A virus infection. J Immunol. 2010, 185: 5056-5065. 10.4049/jimmunol.0902667.View ArticlePubMedGoogle Scholar
- Shioya M, Nishida A, Yagi Y, Ogawa A, Tsujikawa T, Kim-Mitsuyama S, Takayanagi A, Shimizu N, Fujiyama Y, Andoh A: Epithelial overexpression of interleukin-32alpha in inflammatory bowel disease. Clin Exp Immunol. 2007, 149: 480-486. 10.1111/j.1365-2249.2007.03439.x.PubMed CentralView ArticlePubMedGoogle Scholar
- Calabrese F, Baraldo S, Bazzan E, Lunardi F, Rea F, Maestrelli P, Turato G, Lokar-Oliani K, Papi A, Zuin R, Sfriso P, Balestro E, Dinarello CA, Saetta M: IL-32, a novel proinflammatory cytokine in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2008, 178: 894-901. 10.1164/rccm.200804-646OC.View ArticlePubMedGoogle Scholar
- Kobayashi K, Inohara N, Hernandez LD, Galán JE, Núñez G, Janeway CA, Medzhitov R, Flavell RA: RICK/Rip2/CARDIAK mediates signalling for receptors of the innate and adaptive immune systems. Nature. 2002, 416: 194-199. 10.1038/416194a.View ArticlePubMedGoogle Scholar
- Seljelid R, Eskeland T: The biology of macrophages: I General principles and properties. Eur J Haematol. 1993, 51: 267-275.View ArticlePubMedGoogle Scholar
- Kusmartsev S, Gabrilovich DI: Effect of tumor-derived cytokines and growth factors on differentiation and immune suppressive features of myeloid cells in cancer. Cancer Metastasis Rev. 2006, 25: 323-331. 10.1007/s10555-006-9002-6.PubMed CentralView ArticlePubMedGoogle Scholar
- Moeenrezakhanlou A, Shephard L, Lam L, Reiner NE: Myeloid cell differentiation in response to calcitriol for expression CD11b and CD14 is regulated by myeloid zinc finger-1 protein downstream of phosphatidylinositol 3-kinase. J Leukoc Biol. 2008, 84: 519-528. 10.1189/jlb.1207833.View ArticlePubMedGoogle Scholar
- Zhang Y, Zhou B: Functions of thymic stromal lymphopoietin in immunity and disease. Immunol Res. 2012, 52: 211-223. 10.1007/s12026-012-8264-z.PubMed CentralView ArticlePubMedGoogle Scholar
- David-Raoudi M, Deschrevel B, Leclercq S, Galéra P, Boumediene K, Pujol JP: Chondroitin sulfate increases hyaluronan production by human synoviocytes through differential regulation of hyaluronan synthases: Role of p38 and Akt. Arthritis Rheum. 2009, 60: 760-770. 10.1002/art.24302.View ArticlePubMedGoogle Scholar
- Vallières M, du Souich P: Modulation of inflammation by chondroitin sulfate. Osteoarthritis Cartilage. 2010, 18: S1-6.View ArticlePubMedGoogle Scholar
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