Fig. 3

Intracellular signaling pathways of CAP, SNS, and HPA axis for anti-inflammatory responses. Acetylcholine (Ach) can be released from the terminal efferent vagus nerve and further interacts with α7 nicotinic acetylcholine receptor (α7nAChR) on immune cells. Activation of α7nAChR triggers multiple intracellular signaling pathways, including promoting phosphorylation of Janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) pathway, inhibiting Toll-like receptor (TLR)4-myeloid differentiation factor 88 (MyD88)-interleukin-1 receptor-associated kinase (IRAK) cascade as well as declining release of mitochondrial DNA, which contribute to suppression of proinflammatory phenotypes by disturbing activation of nuclear factor-κB (NF-κB) and inflammasomes. The interaction between glucocorticoids and glucocorticoid receptors (GRs) is capable of inhibiting production of proinflammatory cytokines by downregulating NF-κB activity and disturbing c-jun amino-terminal kinase (JNK) cascade after Toll-like receptor (TLR)7 and TLR8 stimulation. Activation of β2-adrenergic receptor with norepinephrine promotes the expression of cyclic AMP (cAMP) and activation of protein kinase A (PKA), which results in decreased production of proinflammatory cytokines by suppressing translocation of NF-κB. It also increases expression of fibroblast growth factor 21 (FGF21) which further suppresses NF-κB activation by promoting activation of extracellular signal regulated kinase (ERK) 1/2-STAT3 cascades in an autocrine manner