Rnf144b alleviates the inflammatory responses and cardiac dysfunction in sepsis

Area of Science:

• Immunology
• Molecular Biology
• Cardiovascular Biology

Background:

• Sepsis is a life-threatening inflammatory condition with high mortality.
• Inflammation is central to sepsis pathogenesis, and its suppression can improve outcomes.
• The role of Rnf144b, an E3 ubiquitin ligase with known anti-inflammatory activity, in sepsis is not well understood.

Purpose of the Study:

• To investigate the function of Rnf144b in the context of sepsis.
• To determine the impact of Rnf144b deficiency in myeloid cells on sepsis progression and cardiac function.

Main Methods:

• Generated myeloid-specific Rnf144b conditional knockout mice.
• Assessed Rnf144b expression in human sepsis patients and LPS-treated macrophages.
• Compared inflammatory cytokine production in wild-type and Rnf144b-deficient macrophages.
• Evaluated survival rates, cardiac function, and signaling pathway activation (TBK1, NF-κB) in septic mice.

Main Results:

• Rnf144b expression was upregulated in sepsis patients and induced by LPS in macrophages.
• Rnf144b deficiency led to increased inflammatory cytokine production.
• Myeloid-specific Rnf144b knockout mice exhibited higher mortality and worsened cardiac dysfunction during sepsis.
• Rnf144b deficiency impaired TBK1 activation but enhanced NF-κB activation.

Conclusions:

• Rnf144b plays a protective role in sepsis by mitigating inflammatory responses.
• Rnf144b deficiency exacerbates sepsis-induced cardiac dysfunction.
• Rnf144b functions, in part, through regulating TBK1 and NF-κB signaling pathways.