Loss of Toll-like receptor 2 and 4 leads to differential induction of endoplasmic reticulum stress and proapoptotic responses in the intestinal epithelium under conditions of XXXX .

@entity32 @entity19 @entity1618 @entity1960 @entity8932 @entity1990 @entity13839
Toll-like receptors (TLRs) play an important role in the recognition of microbial molecular patterns of infectious and commensal bacteria and their expression in various tissues including the intestinal epithelium orchestration of the innate and adaptive immune defense mechanisms. Changes in the TLR signaling pathways due to host genetic predispositions may turn a physiological response into a pathological situation including failure of bacterial clearance and development of @entity32 . The aim of this study was to characterize the role of @entity8932 or @entity1990 deficiency in epithelial cell stress responses under noninflamed and inflamed conditions using TLR-deficient @entity19 and TLR(-/-) cross-bred @entity1618 -deficient @entity19 as a model for genetically driven experimental @entity1960 . Primary intestinal epithelial cells (IEC) were isolated from specific-pathogen-free wild-type, @entity8932 -, @entity1990 -, @entity1618 , IL-10XTLR2- and IL-10XTLR4-deficient @entity19 at the age of 1, 8, and 16 weeks. Histopathological analysis showed absence of tissue pathology (score 0-12) in distal colon sections of @entity8932 - and @entity1990 -deficient @entity19 . In addition, @entity8932 - but not @entity1990 -deficient @entity19 cross-bred to the @entity1618 -deficient background develop moderate @entity1960 , suggesting different effects of these pattern recognition receptors in regulating disease mechanisms. Proteome analysis revealed significantly regulated proteins associated with endoplasmic reticulum (ER) and mitochondrial stress responses in the epithelium. In contrast to @entity8932 (-/-) and IL-10XTLR2(-/-) @entity19 , the induction of the ER-associated chaperone @entity13839 was dissociated from the activation of proapoptotic caspase 3 cleavage in noninflamed @entity1990 (-/-) and IL10XTLR4(-/-) @entity19 . These results suggest that ER-associated cellular stress responses play an important role in epithelial cells homeostasis leading to beneficial but also deleterious effects. We hypothesize that ER stress-associated processes in the absence of @entity8932 and @entity1990 differentially affect host responses and epithelial functions under conditions of genetically driven chronic intestinal @entity32 .
