Stattic

Microglia are the primary immune cells of the central nervous system that play pivotal roles in health and disease. Abnormally activated microglia secrete proinflammatory factors and play essential roles in neurodegenerative disease progression. This study investigated the potential effects of Pentadecyl, rich in odd-numbered fatty acids, such as pentadecanoic acid, isolated from Aurantiochytrium limacinum, on the lipopolysaccharide (LPS)-induced immune response of BV-2 microglial cells.

Cell viability was detected using MTT and LIVE/DEAD assays. mRNA and protein levels of inflammatory cytokines and signaling factors were assessed using real-time PCR and western blotting, respectively.

Pentadecyl did not affect MTT-reducing activity or the number of dead cells stained with ethidium homodimer-1. Pentadecyl selectively mitigated the LPS-induced overproduction of pro-inflammatory cytokines, including interleukin (IL)-6 and IL-1β, at the transcriptional and protein levels, whereas tumor necrosis factor-alpha (TNF-α) expression remained unchanged. Western blot analysis showed that Pentadecyl downregulated the LPS-induced increase in the phosphorylation of signal transducer and activator of transcription 3 (STAT3) but did not affect the phosphorylation of p65, a component of nuclear factor-kappa B, or p38 and c-Jun N-terminal kinase, both of which are mitogen-activated protein kinases. Similar to Pentadecyl, Stattic, a representative STAT3 inhibitor, preferentially suppressed the LPS-induced upregulation of IL-6 and IL-1β mRNA expression, whereas its inhibitory effect on TNF-α expression was relatively modest. These results indicate that Pentadecyl suppresses LPS-induced pro-inflammatory cytokine production without affecting cell survival by regulating the STAT3 signaling pathway in BV-2 cells.

Glioma is marked by swift cell proliferation, extensive invasion and poor outcomes. Serine protease inhibitor H1 (SERPINH1) encoding heat shock protein 47, a collagen-specific molecular chaperone, plays a role in a number of cancers. However, its definite role in glioma remains unclear. The aim of the present study was to investigate the role of SERPINH1 in glioma progression, especially its impact on cell proliferation, migration, invasion and epithelial-mesenchymal transition (EMT). The glioma cell lines LN229, T98, U251 and U87MG were transfected with lentivirus for stable knockdown or overexpression of SERPINH1. Assays assessing cell proliferation, migration and invasion were conducted to investigate the role of SERPINH1 in these processes. Bioinformatic analysis was conducted using The Cancer Genome Atlas and the Chinese Glioma Genome Atlas databases to identify potential molecular pathways associated with SERPINH1. Western blotting (WB) was employed to examine the expression of significant proteins in the JAK1/STAT3 signaling pathway and EMT markers. Nude mice were used for in vivo experiments to evaluate tumor growth and changes related to EMT. Overexpression of SERPINH1 notably increased glioma cell proliferation, migration and invasion, whereas knockdown suppressed these activities. Bioinformatic analyses revealed that SERPINH1 is closely associated with the JAK1/STAT3 signaling pathway and EMT-related genes. WB results confirmed that SERPINH1 regulates the activation of JAK1/STAT3 and influences the levels of EMT markers such as N- and E-cadherin. The JAK1/STAT3 agonist RO8191 partially rescued glioma cell behavior in the SERPINH1 knockdown group, while the inhibitor STATTIC partially weakened the enhanced effects in the SERPINH1 overexpression group. In vivo, SERPINH1 overexpression accelerated tumor growth and EMT progression, while knockdown resulted in a reduction in tumor size and the expression of EMT markers. SERPINH1 is essential for glioma progression, enhancing cell proliferation, migration, invasion and EMT by activating the JAK1/STAT3 signaling pathway. These results indicate that targeting SERPINH1 could provide a promising new approach for glioma therapy.