Table 2 Complex relation between TNF and type I IFN in murine studies
Cross- regulation | Cell type | Activation state | Experimental model | Results | Reference |
|---|---|---|---|---|---|
IFN ↑ ⇒ TNF ↓ | Embryonic fibroblasts (MEF) and macrophages | p38 MAPK stimulus | In vitro stimulation with IFNβ and p38 MAPK stimulus simultaneously | In the presence of a p38 MAPK stimulus, IFNβ induces - via STAT1 activation - TTP, which destabilizes mRNA of several proinflamatory genes including TNFα | [16] |
Macrophages | IFNγ and LPS | Priming by IFNγ, stimulation by LPS in the presence of IFNβ-EF supernatant | IFNβ suppressed LPS/IFNγ induced TNFα production | [26] | |
Synovial tissue | CIA | Daily treatment of CIA using recombinant IFNβ injection (7 days) | FNβ treatment reduced TNFα production in the synovial tissue | [28] | |
IFN ↑ ⇒ TNF ↑ | Macrophages | Healthy | In vitro stimulation with IFNβ | IFNβ mediated upregulation of TNF mRNA | [18] |
IFN ↓ ⇒ TNF ↑ | Macrophages | LPS and IFNγ | EAE in IFNβ KO mice | Increased TNFα production compared with wild-type controls | [23] |
Spleen-derived macrophages | LPS and IFNγ | Cells isolated from IFNβ-deficient mice. Priming by IFNγ with subsequent stimulation with LPS | Increased TNFα production compared with control mice | [24] | |
Synovial tissue | CIA | CIA in IFNβ-deficient mice | Increased TNFα production in synovial of arthritic IFNβ-deficient mice | [24] | |
IFN ↓ ⇒ TNF ↓ | Liver | TNFα-induced lethal shock | IFNAR1 or IFNβ KO mice | Lack of type I IFN signaling protects against TNFα-induced inflammation | [25] |
TNF↓ ⇒ IFN ↑ | Serum | Poly I:C | NZB/W mouse (defect in TNF) injected with poly I:C | NZB/W mice produce more poly I:C- induced IFNα | [22] |