Innate immunity,particularly macrophages,is critical for intestinal homeostasis.Sulforaphane,a dietary isothiocyanate from cruciferous vegetables,has been reported to protect against intestinal inflammation.However,th...Innate immunity,particularly macrophages,is critical for intestinal homeostasis.Sulforaphane,a dietary isothiocyanate from cruciferous vegetables,has been reported to protect against intestinal inflammation.However,the role of macrophages in sulforaphane mediated intestinal inflammation and the underlying molecular mechanisms have not been studied yet.In this study,sulforaphane effectively attenuated dextran sodium sulphate(DSS)induced intestinal inflammation in murine model.Of note,sulforaphane skewed the switching from classically(M1)to alternatively(M2)activated phenotype both in intestinal and bone marrow-derived macrophages(BMDMs).The expression levels of M1 associated maker genes induced by DSS or lipopolysaccharide(LPS)plus interferon gamma-γ(IFN-γ)were suppressed by sulforaphane while M2 marker gene expression levels were improved.This resulted in alteration of inflammatory mediators,particularly interleukin-10(IL-10),both in colon tissues and culture medium of BMDMs.Subsequently,IL-10 was found to mediate the sulforaphane induced M2 phenotype switching of BMDMs through the activation of STAT3 signaling.This was confirmed by immunofluorescence analysis with increased number of p-STAT3-positive cells in the colon sections.Moreover,anti-IL-10 neutralizing antibody significantly interfered M2 phenotyping of BMDMs induced by sulforaphane with reduced STAT3 phosphorylation.Findings here introduced a potential utilization of sulforaphane for intestinal inflammation treatment with macrophages as the therapeutic targets.展开更多
BACKGROUND The Chinese medicine Yangyin Huowei mixture(YYHWM)exhibits good clinical efficacy in the treatment of chronic atrophic gastritis(CAG),but the mechanisms underlying its activity remain unclear.AIM To investi...BACKGROUND The Chinese medicine Yangyin Huowei mixture(YYHWM)exhibits good clinical efficacy in the treatment of chronic atrophic gastritis(CAG),but the mechanisms underlying its activity remain unclear.AIM To investigate the therapeutic effects of YYHWM and its underlying mechanisms in a CAG rat model.METHODS Sprague-Dawley rats were allocated into control,model,vitacoenzyme,and low,medium,and high-dose YYHWM groups.CAG was induced in rats using Nmethyl-N′-nitro-N-nitrosoguanidine,ranitidine hydrochloride,hunger and satiety perturbation,and ethanol gavage.Following an 8-wk intervention period,stomach samples were taken,stained,and examined for histopathological changes.ELISA was utilized to quantify serum levels of PG-I,PG-II,G-17,IL-1β,IL-6,and TNF-α.Western blot analysis was performed to evaluate protein expression of IL-10,JAK1,and STAT3.RESULTS The model group showed gastric mucosal layer disruption and inflammatory cell infiltration.Compared with the blank control group,serum levels of PGI,PGII,and G-17 in the model group were significantly reduced(82.41±3.53 vs 38.52±1.71,23.06±0.96 vs 11.06±0.70,and 493.09±12.17 vs 225.52±17.44,P<0.01 for all),whereas those of IL-1β,IL-6,and TNF-αwere significantly increased(30.15±3.07 vs 80.98±4.47,69.05±12.72 vs 110.85±6.68,and 209.24±11.62 vs 313.37±36.77,P<0.01 for all),and the protein levels of IL-10,JAK1,and STAT3 were higher in gastric mucosal tissues(0.47±0.10 vs 1.11±0.09,0.49±0.05 vs 0.99±0.07,and 0.24±0.05 vs 1.04±0.14,P<0.01 for all).Compared with the model group,high-dose YYHWM treatment significantly improved the gastric mucosal tissue damage,increased the levels of PGI,PGII,and G-17(38.52±1.71 vs 50.41±3.53,11.06±0.70 vs 15.33±1.24,and 225.52±17.44 vs 329.22±29.11,P<0.01 for all),decreased the levels of IL-1β,IL-6,and TNF-α(80.98±4.47 vs 61.56±4.02,110.85±6.68 vs 89.20±8.48,and 313.37±36.77 vs 267.30±9.31,P<0.01 for all),and evidently decreased the protein levels of IL-10 and STAT3 in gastric mucosal tissues(1.11±0.09 vs 0.19±0.07 and 1.04±0.14 vs 0.55±0.09,P<0.01 for both).CONCLUSION YYHWM reduces the release of inflammatory factors by inhibiting the IL-10/JAK1/STAT3 pathway,alleviating gastric mucosal damage,and enhancing gastric secretory function,thereby ameliorating CAG development and cancer transformation.展开更多
基金the financial support provided by“Modern Food Processing,Food Storage,Transportation Technology,and Equipment”State Key Research and Development Plan(2017YFD0400204)the National Science Foundation of China(31972091).
文摘Innate immunity,particularly macrophages,is critical for intestinal homeostasis.Sulforaphane,a dietary isothiocyanate from cruciferous vegetables,has been reported to protect against intestinal inflammation.However,the role of macrophages in sulforaphane mediated intestinal inflammation and the underlying molecular mechanisms have not been studied yet.In this study,sulforaphane effectively attenuated dextran sodium sulphate(DSS)induced intestinal inflammation in murine model.Of note,sulforaphane skewed the switching from classically(M1)to alternatively(M2)activated phenotype both in intestinal and bone marrow-derived macrophages(BMDMs).The expression levels of M1 associated maker genes induced by DSS or lipopolysaccharide(LPS)plus interferon gamma-γ(IFN-γ)were suppressed by sulforaphane while M2 marker gene expression levels were improved.This resulted in alteration of inflammatory mediators,particularly interleukin-10(IL-10),both in colon tissues and culture medium of BMDMs.Subsequently,IL-10 was found to mediate the sulforaphane induced M2 phenotype switching of BMDMs through the activation of STAT3 signaling.This was confirmed by immunofluorescence analysis with increased number of p-STAT3-positive cells in the colon sections.Moreover,anti-IL-10 neutralizing antibody significantly interfered M2 phenotyping of BMDMs induced by sulforaphane with reduced STAT3 phosphorylation.Findings here introduced a potential utilization of sulforaphane for intestinal inflammation treatment with macrophages as the therapeutic targets.
基金Supported by the Project of Regional Collaborative Innovation of Xinjiang Uygur Autonomous Region,No.2022E01008the Graduate Innovation Project of Xinjiang Medical University,No.CXCY2023012.
文摘BACKGROUND The Chinese medicine Yangyin Huowei mixture(YYHWM)exhibits good clinical efficacy in the treatment of chronic atrophic gastritis(CAG),but the mechanisms underlying its activity remain unclear.AIM To investigate the therapeutic effects of YYHWM and its underlying mechanisms in a CAG rat model.METHODS Sprague-Dawley rats were allocated into control,model,vitacoenzyme,and low,medium,and high-dose YYHWM groups.CAG was induced in rats using Nmethyl-N′-nitro-N-nitrosoguanidine,ranitidine hydrochloride,hunger and satiety perturbation,and ethanol gavage.Following an 8-wk intervention period,stomach samples were taken,stained,and examined for histopathological changes.ELISA was utilized to quantify serum levels of PG-I,PG-II,G-17,IL-1β,IL-6,and TNF-α.Western blot analysis was performed to evaluate protein expression of IL-10,JAK1,and STAT3.RESULTS The model group showed gastric mucosal layer disruption and inflammatory cell infiltration.Compared with the blank control group,serum levels of PGI,PGII,and G-17 in the model group were significantly reduced(82.41±3.53 vs 38.52±1.71,23.06±0.96 vs 11.06±0.70,and 493.09±12.17 vs 225.52±17.44,P<0.01 for all),whereas those of IL-1β,IL-6,and TNF-αwere significantly increased(30.15±3.07 vs 80.98±4.47,69.05±12.72 vs 110.85±6.68,and 209.24±11.62 vs 313.37±36.77,P<0.01 for all),and the protein levels of IL-10,JAK1,and STAT3 were higher in gastric mucosal tissues(0.47±0.10 vs 1.11±0.09,0.49±0.05 vs 0.99±0.07,and 0.24±0.05 vs 1.04±0.14,P<0.01 for all).Compared with the model group,high-dose YYHWM treatment significantly improved the gastric mucosal tissue damage,increased the levels of PGI,PGII,and G-17(38.52±1.71 vs 50.41±3.53,11.06±0.70 vs 15.33±1.24,and 225.52±17.44 vs 329.22±29.11,P<0.01 for all),decreased the levels of IL-1β,IL-6,and TNF-α(80.98±4.47 vs 61.56±4.02,110.85±6.68 vs 89.20±8.48,and 313.37±36.77 vs 267.30±9.31,P<0.01 for all),and evidently decreased the protein levels of IL-10 and STAT3 in gastric mucosal tissues(1.11±0.09 vs 0.19±0.07 and 1.04±0.14 vs 0.55±0.09,P<0.01 for both).CONCLUSION YYHWM reduces the release of inflammatory factors by inhibiting the IL-10/JAK1/STAT3 pathway,alleviating gastric mucosal damage,and enhancing gastric secretory function,thereby ameliorating CAG development and cancer transformation.
