MALT1 Knockdown Alleviates Multiorgan Injury and Inflammation Through Inhibiting TAK1/NF-κB Signaling Pathway-Mediated T-Helper 1 and 17 Differentiations in LPS-induced Inflammation.

Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) is a vital regulator of inflammation and innate immune response. The aim of this study was to evaluate the potential of MALT1 knockdown for attenuating lipopolysaccharide (LPS)-induced inflammation. C57BL/6 mice received tail vein injection of knockdown control or Malt1 shRNA, followed by intraperitoneal injection of LPS two weeks later. After 24 h of LPS injection, the mice were euthanized for further analysis. The peripheral naïve CD4+ T cells of mice were isolated, treated with Malt1 overexpression vectors or Malt1 shRNA with or without nuclear factor-κB (NF-κB) activator (PMA) or inhibitor (BAY), under the presence of LPS. MALT1 knockdown alleviated the injuries of kidney and lung tissues, reduced the serum levels of proinflammatory cytokines, and decreased the proportions of T-helper (Th)1 and Th17 cells in mice. The phosphorylation of transforming growth factor beta-activated kinase 1 (TAK1) and NF-κB p65 in the kidney and lung tissues of the mice was hampered by MALT1 knockdown. In vitro experiments showed that MALT1 knockdown decreased Th1 and Th17 differentiation and phosphorylation of TAK1 and NF-κB p65 in naïve CD4+ T cells treated with LPS, while MALT1 overexpression had the opposite effects. The effects of MALT1 knockdown and overexpression on Th1 and Th17 cell differentiation were hampered by PMA and BAY treatment, respectively. MALT1 knockdown alleviates LPS-induced multiorgan injury and inflammation probably through inhibiting the TAK1/NF-κB signaling pathway-mediated Th1 and Th17 differentiation.