Fibrosis Related Inflammatory Mediators: Role of the IL‐10 Cytokine Family

Abstract

Importance of chronic fibroproliferative diseases (FDs) including pulmonary fibrosis, chronic kidney diseases, inflammatory bowel disease, and cardiovascular or liver fibrosis is rapidly increasing and they have become a major public health problem. According to some estimates about 45% of all deaths are attributed to FDs in the developed world. Independently of their etiology the common hallmark of FDs is chronic inflammation. Infiltrating immune cells, endothelial, epithelial, and other resident cells of the injured organ release an orchestra of inflammatory mediators, which stimulate the proliferation and excessive extracellular matrix (ECM) production of myofibroblasts, the effector cells of organ fibrosis. Abnormal amount of ECM disturbs the original organ architecture leading to the decline of function. Although our knowledge is rapidly expanding, we still have neither a diagnostic tool to detect nor a drug to specifically target fibrosis. Therefore, there is an urgent need for the more comprehensive understanding of the pathomechanism of fibrosis and development of novel diagnostic and therapeutic strategies. In the present review we provide an overview of the common key mediators of organ fibrosis highlighting the role of interleukin-10 (IL-10) cytokine family members (IL-10, IL-19, IL-20, IL-22, IL-24, and IL-26), which recently came into focus as tissue remodeling-related inflammatory cytokines.

The pattern of IL-24/mda-7 and its cognate receptors expression following activation of human hepatic stellate cells

“…The possible role of IL-10 family members such as IL-20, IL-22 and, more recently, IL-24/mda-7, started to be delineated more in fibrosis development (13). Even though the general player molecules involved in HSC cell activation and transition into myofibroblasts have been studied deeply, the possible role of IL-24/mda7 needs to be investigated in liver fibrosis.…”

“…Although, expression level of IL-20 and IL-22 were evaluated in human and mice stellate cells, comparing IL-24/mda-7 expression in normal or activated HSCs is rare (13,26). New research revealed that IL-22, another member of the IL-10 cytokine family, promotes HSC proliferation and activation, prevents HSC apoptosis, induces the overexpression of HSC growth factors and fibrosis markers including Col-IV, laminin and hyaluronic acid (27).…”

“…The expression of IL-20R2 and IL-22R1 was also investigated elsewhere, and IL-22R1 expression was reported to be distributed among the kidney, liver, pancreas and skin (13).…”

“…As IL-24/mda-7 exhibits characteristics of apoptosis induction in transforming cells, its utility for cancer gene therapy approaches in heavy is considered by several groups (16,17). Furthermore, a recent study has indicated that the IL-10 cytokine family can be effective in ECM production with a pivotal role in fibrosis, but the underlying mechanism by which IL-24/mda-7 may inhibit ECM production, is still unknown (13).…”

“…(11,12). It serves an important role in fibroproliferative diseases, including pulmonary fibrosis, chronic kidney diseases, inflammatory bowel diseases and cardiovascular diseases (13).…”