Chitinase-3-like-1 (Chi3l1), also known as YKL-40 or BRP-39, is a highly conserved mammalian chitinase with a chitin-binding ability but no chitinase enzymatic activity. Chi3l1 is secreted by various cell types and induced by several inflammatory cytokines. It can mediate a series of cell biological processes, such as proliferation, apoptosis, migration, differentiation, and polarization. Accumulating evidence has verified that Chi3l1 is involved in diverse inflammatory conditions; however, a systematic and comprehensive understanding of the roles and mechanisms of Chi3l1 in almost all human body system-related inflammatory diseases is still lacking. The human body consists of ten organ systems, which are combinations of multiple organs that perform one or more physiological functions. Abnormalities in these human systems can trigger a series of inflammatory environments, posing serious threats to the quality of life and lifespan of humans. Therefore, exploring novel and reliable biomarkers for these diseases is highly important, with Chi3l1 being one such parameter because of its physiological and pathophysiological roles in the development of multiple inflammatory diseases. Reportedly, Chi3l1 plays an important role in diagnosing and determining disease activity/severity/prognosis related to multiple human body system inflammation disorders. Additionally, many studies have revealed the influencing factors and regulatory mechanisms (e.g., the ERK and MAPK pathways) of Chi3l1 in these inflammatory conditions, identifying potential novel therapeutic targets for these diseases. In this review, we comprehensively summarize the potential roles and underlying mechanisms of Chi3l1 in inflammatory disorders of the respiratory, digestive, circulatory, nervous, urinary, endocrine, skeletal, muscular, and reproductive systems, which provides a more systematic understanding of Chi3l1 in multiple human body system-related inflammatory diseases. Moreover, this article summarizes potential therapeutic strategies for inflammatory diseases in these systems on the basis of the revealed roles and mechanisms mediated by Chi3l1.

Angiotensin II (Ang II) is a principal molecule of the renin‑angiotensin system, which promotes hypertrophy and fibrosis. It has been demonstrated that Ang II upregulates the expression of cyclophilin A (CypA), which is a potential myocardial hypertrophy factor. However, the mechanisms by which Ang II induces the expression of CypA in cardiomyocytes remain unclear. In the present study, reactive oxygen species (ROS) were detected by fluorescence microscopy, and western blot analysis and ELISA were used to measure CypA expression. It was identified that Ang II enhanced the production of ROS in rat cardiomyocytes. ROS, in turn, promoted CypA expression and secretion. Notably, the action of Ang II was primarily dependent on the angiotensin type 2 receptor (AT2R), not the type 1 receptor. These results provided an insight into the role of the AT2R signaling pathway in Ang II‑induced myocardial hypertrophy.

Microplitis bicoloratus bracovirus (MbBV) induces apoptosis in hemocytes of the host (Spodoptera litura) via the cyclophilin A (CypA)‐mediated signaling pathway. However, the mechanisms underlying CypA‐mediated signaling during apoptosis remain largely unknown. Therefore, in this study, we investigated how CypA and apoptosis‐inducing factor (AIF) interact during MbBV‐mediated apoptosis. Our findings showed that MbBV induces apoptosis through the CypA‐AIF axis of insect immune suppression. In MbBV‐infected Spli221 cells, both the expression of the cypa gene and the release of AIF from the mitochondria increased the number of apoptotic cells. CypA and AIF underwent concurrent cytoplasm‐nuclear translocation. Conversely, blocking of AIF release from mitochondria not only inhibited the CypA‐AIF interaction but also inhibited the cytoplasmic‐nuclear translocation of AIF and CypA. Importantly, the survival of the apoptotic phenotype was significantly rescued in MbBV‐infected Spli221 cells. In addition, we found that the cyclosporine A‐mediated inhibition of CypA did not prevent the formation of the CypA and AIF complex; rather, this only suppressed genomic DNA fragmentation. In vitro experiments revealed direct molecular interactions between recombinant CypA and AIF. Taken together, our results demonstrate that the CypA‐AIF interaction plays an important role in MbBV‐induced innate immune suppression. This study will help to clarify aspects of insect immunological mechanisms and will be relevant to biological pest control.

Cyclophilin D (CypD) is regulated during the innate immune response of insects. However, the mechanism by which CypD is activated under innate immunosuppression is not understood. Microplitis bicoloratus bracovirus (MbBV), a symbiotic virus in the parasitoid wasp, Microplitis bicoloratus, suppresses innate immunity in parasitized Spodoptera litura. Here, we demonstrate that MbBV promotes the CypD acetylation of S. litura, resulting in an immunosuppressive phenotype characterized by increased apoptosis of hemocytes and MbBV-infected cells. Under MbBV infection, the inhibition of CypD acetylation significantly rescued the apoptotic cells induced by MbBV, and the point-mutant fusion proteins of CypDK125R-V5 were deacetylated. The CypD-V5 fusion proteins were acetylated in MbBV-infected cells. Deacetylation of CypDK125R-V5 can also suppress the MbBV-induced increase in apoptosis. These results indicate that CypD is involved in the MbBV-suppressed innate immune response via the CypD-acetylation pathway and S. litura CypD is acetylated on K125.