Poly-gamma-glutamic acid(γ-PGA)is a natural,edible and non-toxic polymer synthesized by Bacillus subtilis and is suggested as a safe biomaterial for the use in hydrogels and vaccine adjuvants.However,the effect ofγ-...Poly-gamma-glutamic acid(γ-PGA)is a natural,edible and non-toxic polymer synthesized by Bacillus subtilis and is suggested as a safe biomaterial for the use in hydrogels and vaccine adjuvants.However,the effect ofγ-PGA on inflammasome activation has not yet been studied in macrophages.Inflammasomes,which are intracellular multi-protein complexes,promote acute and chronic inflammation via interleukin-1βor interleukin-18 maturation,and they are known targets for metabolic syndromes and cancer.In this study,we observed thatγ-PGA attenuated NLRP3,NLRC4 and AIM2 inflammasome activation,whereas it upregulated pro-inflammatory cytokine expression in human and murine macrophages.Althoughγ-PGA had conflicting effects on cytokine production and maturation,it clearly alleviated the severity of lipopolysaccharide-induced endotoxin shock in an animal model.Thus,we suggestγ-PGA as a candidate to control inflammasome-mediated disorders.展开更多
Lactoferrin （LF） and retinoic acid （RA） are enriched in colostrum, milk, and mucosal tissues. We recently showed that LF-induced IgA class switching through binding to betaglycan （transforming growth factor-beta ...Lactoferrin （LF） and retinoic acid （RA） are enriched in colostrum, milk, and mucosal tissues. We recently showed that LF-induced IgA class switching through binding to betaglycan （transforming growth factor-beta receptor III, TpRIII） and activation of canonical TGF-p signaling. We investigated the combined effect of LF and RA on the overall IgA response. An increase in IgA production by LF was further augmented by RA. This combination effect was also evident in Ig germ-line α （GLa） transcription and GLa promoter activity, indicating that LF in cooperation with RA increased IgA isotype switching. We subsequently found that RA enhanced TβRIII expression and that this increase contributed to LF-stimulated IgA production. In addition to the IgA response, LF and RA in combination also enhanced the expression of the gut-homing molecules C-C chemokine receptor 9 （CCR9） and a4β7 on B cells. Finally, peroral administration of LF and RA enhanced the frequency of CCR9＋ IgA＋ plasma cells in the lamina propria. Taken together, these results suggest that LF in cooperation with RA can contribute to the establishment of gut IgA responses.展开更多
基金We thank Young Jin Kim(Korea Food Research Institute)for providing the cheonggukjang extractsThis research was supported by the Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Education,Science and Technology(NRF-2015R1A2A2A01004183).
文摘Poly-gamma-glutamic acid(γ-PGA)is a natural,edible and non-toxic polymer synthesized by Bacillus subtilis and is suggested as a safe biomaterial for the use in hydrogels and vaccine adjuvants.However,the effect ofγ-PGA on inflammasome activation has not yet been studied in macrophages.Inflammasomes,which are intracellular multi-protein complexes,promote acute and chronic inflammation via interleukin-1βor interleukin-18 maturation,and they are known targets for metabolic syndromes and cancer.In this study,we observed thatγ-PGA attenuated NLRP3,NLRC4 and AIM2 inflammasome activation,whereas it upregulated pro-inflammatory cytokine expression in human and murine macrophages.Althoughγ-PGA had conflicting effects on cytokine production and maturation,it clearly alleviated the severity of lipopolysaccharide-induced endotoxin shock in an animal model.Thus,we suggestγ-PGA as a candidate to control inflammasome-mediated disorders.
文摘Lactoferrin （LF） and retinoic acid （RA） are enriched in colostrum, milk, and mucosal tissues. We recently showed that LF-induced IgA class switching through binding to betaglycan （transforming growth factor-beta receptor III, TpRIII） and activation of canonical TGF-p signaling. We investigated the combined effect of LF and RA on the overall IgA response. An increase in IgA production by LF was further augmented by RA. This combination effect was also evident in Ig germ-line α （GLa） transcription and GLa promoter activity, indicating that LF in cooperation with RA increased IgA isotype switching. We subsequently found that RA enhanced TβRIII expression and that this increase contributed to LF-stimulated IgA production. In addition to the IgA response, LF and RA in combination also enhanced the expression of the gut-homing molecules C-C chemokine receptor 9 （CCR9） and a4β7 on B cells. Finally, peroral administration of LF and RA enhanced the frequency of CCR9＋ IgA＋ plasma cells in the lamina propria. Taken together, these results suggest that LF in cooperation with RA can contribute to the establishment of gut IgA responses.
