Skip to main content
. 2022 Jun 16;13:871997. doi: 10.3389/fpsyt.2022.871997

FIGURE 1.

FIGURE 1

Pro-inflammatory pathways in microglia. (A) TNF-α receptor activation, induces the canonical pro-inflammatory transcriptional factors such as NFκB and subsequent production of inflammatory mediators. This pathway can be inhibited by Infliximab. (B) TLR4 ligands and secreted Gal-3 directly bind to TLR4 on the microglial surface and exacerbates inflammatory responses through induction of different cytokines and chemokines. This pathway can be inhibited by Ibudilast. (C) Activation of INF-γ receptor on microglia triggers the overexpression of inducible nitric oxide synthase (iNOS) and overproduction of nitric oxide via Janus kinase (JAK)/signal transducer and activator of transcription (STAT)/RIF-1 pathway. Corticosteroids can suppress this pathway at the level of STAT factors. (D) IL-6 trans-signaling occurs in brain cell types that have membrane bound gp130, including microglia. IL-6 bound to soluble IL-6R activates signaling through membrane bound gp130. This trans-signaling is thought to be pro-inflammatory via the induction of JAK/STAT and MAPK signaling pathways. Tocilizumab inhibits this pro-inflammatory pathway. TNF-α, tumor necrosis factor-α; IKK, the IκB kinase; NO, nitric oxide; iNOS, inducible nitric oxide synthase; IL-1β, interleukin 1 beta; IL-6, interleukin 6; JAK, Janus kinase; STAT, signal transducer and activator of transcription; RIF-1, replication timing regulatory factor 1; MAPK, a mitogen-activated protein kinase; TLR4, toll-like receptor 4; MYD88, myeloid differentiation primary response 88; TRIF, TIR-domain-containing adapter-inducing interferon-β; IRAK, interleukin 1 receptor associated kinase; TRAF, TNF receptor associated factor; IFN-β, interferon-β; IFN-γ, interferon gamma.