The roles of SOCS3 and STAT3 in bacterial infection and inflammatory diseases

Abstract

The suppressor of cytokine signalling-3 (SOCS3) is well known as a feedback inhibitor of the Janus kinases-signal transducer and activator of transcription 3 (JAK/STAT3) signalling pathway, which mediates the signal transduction of many cytokines, growth factors and hormones during many cellular processes. The critical role of SOCS3 is manifested by its binding to both the JAK kinase and the cytokine receptor, which can result in the inhibition of STAT3 phosphorylation. STAT3 triggers variety of genes expression in response to cytokine (IL-6 family, IL-10) and growth factor stimulation and thus plays a critical role in many cellular biological processes involved in anti/pro-inflammatory responses, cell growth and cell death. SOCS3 might act directly either by hampering JAK activation or by mediating the ubiquitination and subsequent proteasome degradation of the cytokine/growth factor/hormone receptor. Generally, SOCS3 is a negative regulator for cytokine or hormone signalling. But in some cases, SOCS3 regulates the inflammatory responses positively through inhibiting STAT3. An increasing number of reports showed abnormal expression levels of SOCS3/STAT3 in different myeloid and lymphoid cells as well as in various non-hematopoietic cells, which suggested its involvement in various infection and inflammatory diseases. In this review, we described the role of SOCS3 and STAT3 expression in different cell populations in regulating the outcomes of infection and inflammatory diseases.

Keywords: JAK; SOCS; SOCS3; STAT3; bacterial infection; cytokines; inflammation.