CTH/H2S Regulates LPS-Induced Inflammation through IL-8 Signaling in MAC-T Cells

Abstract

Hydrogen sulfide (H2S), as an endogenous gaseous signaling molecule, plays an important role in the inflammatory process. Our previous study found that Cystathionine-γ-lyase (CTH) and H2S are correlated with the occurrence and development of Clinical Mastitis (CM) in Holstein cows. However, the functions and regulatory mechanisms of CTH/H2S are still unknown. In this study, the inflammatory mammary cell model based on the MAC-T cell line was established by Lipopolysaccharide (LPS)-induced manner to further explore the function and regulatory mechanism of CTH/H2S in cows with CM. In the inflammatory MAC-T cell, the CTH expression and H2S production were both repressed in an LPS-dose dependent manner, which demonstrated that CTH/H2S is related to the progression of inflammation. The inhibition of CTH/H2S using a selective CTH inhibitor, β-cyano-L-Alanine (BCA), promoted LPS-induced inflammation response and the expression of inflammatory cytokines. However, this was reversed by the H2S donor NaHS, demonstrating that H2S can protect cells from inflammatory damage. Intriguingly, interleukin-8 (IL-8) showed an inverse expression pattern correlated with the H2S-mediated cell protection effect during the inflammation process, and the inhibition test using a selective IL-8 receptor antagonist, SB225002, showed that IL-8 signaling plays a critical role in mediating endogenous H2S synthesis, and CTH/H2S exerts its anti-inflammation via IL-8-mediated signaling. This study provided support for the prevention and treatment of CM and the development of a novel anti-inflammatory strategy.

The potential anti-inflammatory and anti-apoptotic influence of hydrogen sulfide on xenoestrogen induced-toxicity in rats

“…The results showed that the value of serum Il-6 was significantly increased after XE treatment, and NaHS adding display marked decrease in serum IL-6 level. This data is consistent with previous reports(Lin et al, 2022) showed that H2S exhibited an antiinflammatory effect on various tissues and organs in mammals(Ali et al, 2018), vascular inflammation(Martelli et al, 2021), cardiovascular inflammation(Sikura et al, 2019;, and airway inflammation(Bazhanov et al, 2017). However,Sağlam et al (2017) showed that NaHS addition did not show any decrease in IL-6 levels.…”