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Loss of LAT1 sex-dependently delays recovery after caerulein-induced acute pancreatitis

World Journal of Gastroenterology 2022年第10期28卷 1024-1054页

作者： Cristina M Hagen eva roth Theresia Reding Graf François Verrey Rolf Graf Anurag Gupta Giovanni Pellegrini Nadège Poncet Simone Mafalda Rodrigues Camargo Institute of Physiology University of ZurichZurich 8057ZHSwitzerland Swiss Hepato-Pancreato-Biliary Center Department of Visceral and Transplantation SurgeryZurich University HospitalZurich 8091ZHSwitzerland Institute of Veterinary Pathology University of ZurichZurich 8057ZHSwitzerland

BACKGROUND The expression of amino acid transporters is known to vary during acute pancreatitis(AP)except for LAT1(slc7a5),the expression of which remains ***1 supports cell growth by importing leucine and thereby stimulates mammalian target of rapamycin(mTOR)activity,a phenomenon often observed in cancer *** mechanisms by which LAT1 influences physiological and pathophysiological processes and affects disease progression in the pancreas are not yet *** To evaluate the role of LAT1 in the development of and recovery from *** AP was induced with caerulein(cae)injections in female and male mice expressing LAT1 or after its knockout(LAT1 Cre/LoxP).The development of the initial AP injury and its recovery were followed for seven days after cae injections by daily measuring body weight,assessing microscopical tissue architecture,mRNA and protein expression,protein synthesis,and enzyme activity levels,as well as by testing the recruitment of immune cells by FACS and *** The initial injury,evaluated by measurements of plasma amylase,lipase,and trypsin activity,as well as the gene expression of dedifferentiation markers,did not differ between the ***,early metabolic adaptations that support regeneration at later stages were blunted in LAT1 knockout *** in females,we observed less mTOR reactivation and dysfunctional *** later regeneration phase was clearly delayed in female LAT1 knockout mice,which did not regain normal expression of the pancreas-specific differentiation markers recombining binding protein suppressor of hairless-like protein(rbpjl)and basic helixloop-helix family member A15(mist1).Amylase mRNA and protein levels remained lower,and,strikingly,female LAT1 knockout mice presented signs of fibrosis lasting until day *** contrast,pancreas morphology had returned to normal in wild-type *** LAT1 supports the regeneration of acinar cells after *** mice lacking LAT1 exh

关键词： Acute pancreatitis Amino acid transporter LAT1 Metabolism Regeneration Fibrosis

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CREMa overexpression decreases IL-2 production,induces a TH17 phenotype and accelerates autoimmunity

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Journal of Molecular Cell Biology 2012年第2期4卷 121-123页

作者： Ralph Lippe Kim Ohl Georg Varga Thomas Rauen Jose C.Crispin Yuang-Taung Juang Stefanie Kuerten Frank Tacke Marc Wolf Kirsten Roebrock Thomas Vogl eva Verjans Nora Honke Jan Ehrchen Dirk Foell Boris Skryabin Norbert Wagner George C.Tsokos Johannes roth Klaus Tenbrock Institute of Immunology Interdisciplinary Center for Clinical Research(IZKF)University of MuensterMuensterGermany IZKF Research Group 5 Interdisciplinary Center for Clinical Research(IZKF)University of MuensterMuensterGermany Department of Pediatrics RWTH Aachen UniversityAachenGermany Beth Israel Deaconess Hospital Harvard Medical SchoolBostonMAUSA Department of Medicine II RWTH Aachen UniversityAachenGermany Institute of Anatomy University of CologneCologneGermany Department of Medicine III RWTH Aachen UniversityAachenGermany Department of Dermatology Interdisciplinary Center for Clinical Research(IZKF)University of MuensterMuensterGermany Institute of Experimental Pathology(ZMBE) Interdisciplinary Center for Clinical Research(IZKF)University of MuensterMuensterGermany Interdisciplinary Center for Clinical Research(IZKF)Aachen RWTH Aachen UniversityGermany

Dear Editor,External cytokines produced by cells of the innate immune system induce the dif-ferentiation of CD4+T cells into helper T cell subsets with distinct functions and cytokine *** from TH1 and TH2 cells a third subset of helper T cells has been described,which is characterized by increased expression of IL-17A,IL-17F,IL-21 and IL-22(TH17 cells).

关键词： TH17 induce cytokines

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