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MFHAS1 Is Associated with Sepsis and Stimulates TLR2/NF-κB Signaling Pathway Following Negative Regulation

Jing Zhong1, Qi-Qing Shi2, Min-Min Zhu1

  • 1Department of Anesthesiology, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.

Plos One
|November 25, 2015
PubMed

Insights

Malignant fibrous histiocytoma amplified sequence 1 (MFHAS1) is elevated in sepsis patients and influences Toll-like receptor 2 (TLR2) signaling. MFHAS1 initially inhibits, then stimulates inflammation via the TLR2/NF-κB pathway.

Area of Science:

  • Immunology
  • Molecular Biology
  • Sepsis Pathophysiology

Background:

  • Malignant fibrous histiocytoma amplified sequence 1 (MFHAS1) has potential immunoregulatory roles via Toll-like receptors (TLRs).
  • Toll-like receptor 2 (TLR2) is implicated in sepsis-related inflammation, cardiac dysfunction, and acute kidney injury.
  • The specific role of MFHAS1 in TLR2-mediated sepsis remains uninvestigated.

Purpose of the Study:

  • To investigate the association between MFHAS1 and sepsis.
  • To elucidate the impact of MFHAS1 on the TLR2 signaling pathway in sepsis.

Main Methods:

  • Blood samples from sepsis patients and controls were analyzed for MFHAS1 levels.
  • HEK 293 cells, RAW 264.7 macrophages, and THP-1 monocytes were used to study MFHAS1's effect on TLR2 signaling.
  • TLR2 ligand Pam3CSK4 was used to stimulate cells and assess MFHAS1 production and downstream signaling.

Main Results:

  • Blood MFHAS1 levels were significantly higher in sepsis patients, particularly in mononuclear cells.
  • Pam3CSK4 induced MFHAS1 production in macrophages and monocytes in a time-dependent manner.
  • MFHAS1 exhibited biphasic effects on TLR2 signaling and inflammation: inhibitory at 6 hours, stimulatory after 24 hours, activating TLR2/NF-κB, JNK, and p38 pathways.

Conclusions:

  • MFHAS1 is upregulated in sepsis and modulates TLR2 signaling.
  • MFHAS1 plays a complex, time-dependent role in sepsis-induced inflammation.
  • These findings suggest MFHAS1 as a potential therapeutic target in sepsis management.

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