There are several AP binding

There are several AP-1 Ciprofibrate in the sequence of TIMP-1 promoter [18,19]. EBV could up-regulate TIMP-1 expression by binding to the AP-1 site in the TIMP-1 promoter [18]. IL-32, a newly multi-function cytokine, could activate AP-1, NF-κβ, p38MAPK signal pathways, and induce cytokine expressions, such as IL-1β, TNF-α, and IL-8. [13,27]. Furthermore, hepatic IL-32 expression level is positively associated with liver fibrosis which is resulted by HBV or HCV infection [16,17]. However, the role of IL-32 in fibrogenesis is not thoroughly clear. In the present study, we found that IL-32 could induce TIMP-1 expression by HSCs at a dose-dependent manner. Moreover, TIMP-1 expression induced by IL-32 is mediated through activation of AP-1 signal pathway. The increased TIMP-1 expression could promote the migration of HSCs. Taken together, we believe that IL-32 might be involved in the fibrogenesis by inducing TIMP-1 expression and promoting HSCs migration. However, the detailed signal transduction pathway is not fully elaborated. Liver fibrosis is a necessary stage from the progression of chronic liver diseases to cirrhosis [1]. Cirrhosis, the end-stage of liver fibrosis, could result in life-threatening complications, such as liver failure, portal hypertension, and hepatocellular carcinoma. [31]. Unfortunately, there are not effective drugs to cure liver fibrosis worldwide. Fortunately, liver fibrosis could be reversed, and recovery from the established experimental fibrosis could occur [28]. So it is very important to elucidate the mechanism of liver fibrosis in order to halt or lessen the progression of liver fibrosis. In the present study, we found that IL-32 could induce TIMP-1 expression by HSCs through activating AP-1 signal pathway, and the increased TIMP-1 expression could promote the migration of HSCs. Because IL-32 is an important pro-inflammatory cytokine [32], and because HBV, HCV could induce IL-32 by hepatocytes [17,23], and because liver fibrosis is initiated by liver cells damage [4] which mainly results from virus infection, we think that IL-32 might be a new therapy target for hepatic fibrosis as well as hepatitis. However, the detailed mechanism is not thoroughly elucidated. Subsequently, we will further research the role of IL-32 in the fibrogenesis and hepatitis.
Conflict of interest
Acknowledgments This study was funded by research grants from the National Natural Science Foundation of China (Grant No. 81401306), Doctoral Startup Foundation of the Third Affiliated Hospital of Guangzhou Medical University (No. 2014Y02), and Guangdong Medical Research Foundation (No. A2014318).
Introduction Osteoarthritis (OA) is a degenerative joint disease characterized by articular cartilage destruction and subsequent involvement of various other issues, following the accumulation of mechanical stress on joints. Many factors including inflammation, aging, genetic factors and pathological chondrocyte hypertrophy are involved in the onset and progression of OA. Destruction of articular cartilage in OA is caused by a disruption of cartilage homeostasis. Matrix-degrading enzymes are considered to play key roles in the degradation of cartilage matrix proteins and matrix metalloproteinases (MMPs), such as MMP-1, -2, -8 -9 and 13 are elevated in human OA cartilage and synovium [[1], [2], [3]]. Among these MMPs, MMP-13 is most predominantly implicated in cartilage degradation during OA because it is the primary protein that cleaves type II collagen, the most abundant component of articular cartilage [4]. MMP-13 transgenic mice exhibit articular cartilage degradation and joint pathology that resembles OA [5]. MMP is considered an excellent therapeutic target for inhibiting cartilage damage in OA. However, the clinical usefulness of broad spectrum MMP inhibitors is restricted by their musculoskeletal side effects [6]. In contrast, more targeted inhibition of MMPs, such as MMP-13 inhibition, does not produce sufficient effect [[7], [8], [9]].