ABSTRACT
OBJECTIVE: To investigate the mechanism of action of fatty acid receptors, FFAR1 and FFAR4, on ulcerative colitis (UC) through fatty acid metabolism and macrophage polarization. METHODS: Dextran sulfate sodium (DSS)-induced mouse model of UC mice was used to evaluate the efficacy of FFAR1 (GW9508) and FFAR4 (GSK137647) agonists by analyzing body weight, colon length, disease activity index (DAI), and histological scores. Real-time PCR and immunofluorescence analysis were performed to quantify the levels of fatty acid metabolizing enzymes and macrophage makers. FFA-induced lipid accumulation in RAW264.7 cells was visualized by Oil Red O staining analysis, and cells were collected to detect macrophage polarization by flow cytometry. RESULTS: The combination of GW9508 and GSK137647 significantly improved DSS-induced UC symptoms, caused recovery in colon length, and decreased histological injury. GW9508 + GSK137647 treatment upregulated the expressions of CD206, lipid oxidation enzyme (CPT-1α) and anti-inflammatory cytokines (IL-4, IL-10, IL-13) but downregulated those of CD86, lipogenic enzymes (ACC1, FASN, SCD1), and pro-inflammatory cytokines (IL-1ß, IL-6, TNF-α). Combining the two agonists decreased FFA-induced lipid accumulation and increased CD206 expression in cell-based experiments. CONCLUSION: Activated FFAR1 and FFAR4 ameliorates DSS-induced UC by promoting fatty acid metabolism to reduce lipid accumulation and mediate M2 macrophage polarization.
Subject(s)
Colitis, Ulcerative , Fatty Acids, Nonesterified , Macrophages , Receptors, G-Protein-Coupled , Animals , Mice , Aniline Compounds/pharmacology , Aniline Compounds/therapeutic use , Colitis, Ulcerative/chemically induced , Colitis, Ulcerative/drug therapy , Colon/pathology , Cytokines/metabolism , Dextran Sulfate , Disease Models, Animal , Fatty Acids, Nonesterified/metabolism , Macrophages/drug effects , Macrophages/metabolism , Methylamines/pharmacology , Methylamines/therapeutic use , Mice, Inbred C57BL , Propionates/pharmacology , Propionates/therapeutic use , Sulfonamides/pharmacology , Sulfonamides/therapeutic use , Receptors, G-Protein-Coupled/agonistsABSTRACT
Objective:To investigate the early clinical features and diagnosis of granulomatous polyangiitisï¼GPAï¼ with head and neck symptoms as the first presentation. Methods:The data of 28 patients with GPA diagnosed in the Second Hospital of Shanxi Medical University from 2014 to 2021, whose first symptoms appeared on the head and neck, were collected. All patients underwent relevant imaging examinations, laboratory tests, endoscopy, and pathological tissue biopsies. Systemic glucocorticoid or combined immunosuppressive therapy was administered and followed up for 1-5 years. Results:Two patients refused treatment and were lost to follow-up; 26 patients were discharged with improved symptoms, complaining of nasal ventilation, resolution of supraorbital swelling, reduced dyspnoea, and renal symptoms. Five patients were repeatedly admitted to the hospital due to recurrent renal involvement. Conclusion:Although GPA often begins with head and neck symptoms, it is non-specific and can easily be confused with chronic inflammatory disease, leading to misdiagnosis. If suspicious cases are identified, they should be combined with endoscopy, pathological tissue biopsy, and special laboratory tests as early as possible to shorten the time to diagnosis, and obtain early diagnosis and treatment.
