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SR-A1 suppresses colon inflammation and tumorigenesis through negative regulation of NF-κB signaling

Guijuan Zong1, Yaqin Zhu2, Yan Zhang2

  • 1Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China; Department of Pathology, Nantong University Affiliated Tumor Hospital, Nantong, Jiangsu, People's Republic of China.

Biochemical Pharmacology
|June 4, 2018
PubMed

Insights

Macrophage scavenger receptor class A1 (SR-A1) suppresses inflammatory bowel disease and colitis-associated cancer. SR-A1 deficiency exacerbates colitis by activating NF-κB signaling in the colon.

Area of Science:

  • Immunology
  • Gastroenterology
  • Molecular Biology

Background:

  • Inflammatory bowel disease (IBD) involves chronic intestinal inflammation and increases colorectal cancer risk.
  • Mechanisms underlying IBD pathogenesis remain incompletely understood.
  • Macrophage scavenger receptor class A1 (SR-A1) is a pattern recognition receptor crucial in immune responses.

Purpose of the Study:

  • To investigate the role of SR-A1 in colitis and its underlying mechanisms.
  • To determine SR-A1's effect on dextran sodium sulfate (DSS)-induced colitis.
  • To explore SR-A1's impact on colitis-associated cancer.

Main Methods:

  • Utilized SR-A1 knockout (SR-A1-/-) and wild-type mice.
  • Induced acute and recurring colitis using dextran sodium sulfate (DSS).
  • Analyzed NF-κB signaling pathways (canonical and noncanonical) and TRAF3 interactions in macrophages.

Main Results:

  • SR-A1-/- mice exhibited exacerbated DSS-induced colitis.
  • Colitis severity correlated with robust activation of canonical and noncanonical NF-κB signaling.
  • SR-A1 deficiency led to increased colitis-associated cancer.
  • SR-A1 suppressed noncanonical NF-κB signaling, potentially via TRAF3 interaction.

Conclusions:

  • SR-A1 acts as a crucial suppressor of inflammatory bowel disease.
  • SR-A1 mitigates colitis and associated cancer development.
  • Targeting SR-A1 may offer therapeutic strategies for IBD.
Keywords:
Azoxymethane (Pubchem CID: 33184)Class A scavenger receptorColitisDextran sodium sulfate (Pubchem CID: 5167213)MacrophageNF-κB signaling

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