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Toll-like receptor (TLR) 2 induced through TLR4 signaling initiated by Helicobacter pylori cooperatively amplifies iNOS induction in gastric epithelial cells.

Abstract

Cell-surface Toll-like receptors (TLRs) initiate innate immune responses, such as inducible nitric oxide synthase (iNOS) induction, to microorganisms' surface pathogens. TLR2 and TLR4 play important roles in gastric mucosa infected with Helicobacter pylori (H. pylori), which contains lipopolysaccharide (LPS) as a pathogen. The present study investigates their physiological roles in the innate immune response of gastric epithelial cells to H. pylori-LPS. Changes in the expression of iNOS, TLR2, and TLR4, as well as downstream activation of mitogen-activated protein kinases and nuclear factor-kappaB (NF-kappaB), were analyzed in normal mouse gastric mucosal GSM06 cells following stimulation with H. pylori-LPS and interferon-gamma. Specific inhibitors for mitogen-activated protein kinases, NF-kappaB, and small interfering RNA for TLR2 or TLR4 were employed. The immunohistochemistry of TLR2 was examined in human gastric mucosa. H. pylori-LPS stimulation induced TLR2 in GSM06 cells, but TLR4 was unchanged. TLR2 induction resulted from TLR4 signaling that propagated through extracellular signal-related kinase and NF-kappaB activation, as corroborated by the decline in TLR4 expression on small interfering RNA treatment and pretreatment with inhibitors. The induction of iNOS and the associated nitric oxide production in response to H. pylori-LPS stimulation were inhibited by declines in not only TLR4 but also TLR2. Increased expression of TLR2 was identified in H. pylori-infected human gastric mucosa. TLR4 signaling initiated by H. pylori-LPS and propagated via extracellular signal-regulated kinase and NF-kappaB activation induced TLR2 expression in gastric epithelial cells. Induced TLR2 cooperated with TLR4 to amplify iNOS induction. This positive correlation may constitute a mechanism for stimulating the innate immune response against various bacterial pathogens, including H. pylori-LPS.

Authors+Show Affiliations

Research Project of Biofunctional Reactive Species, Yamagata Promotional Organization for Industrial Technology, Yamagata, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17855767

Citation

Uno, Kaname, et al. "Toll-like Receptor (TLR) 2 Induced Through TLR4 Signaling Initiated By Helicobacter Pylori Cooperatively Amplifies iNOS Induction in Gastric Epithelial Cells." American Journal of Physiology. Gastrointestinal and Liver Physiology, vol. 293, no. 5, 2007, pp. G1004-12.
Uno K, Kato K, Atsumi T, et al. Toll-like receptor (TLR) 2 induced through TLR4 signaling initiated by Helicobacter pylori cooperatively amplifies iNOS induction in gastric epithelial cells. Am J Physiol Gastrointest Liver Physiol. 2007;293(5):G1004-12.
Uno, K., Kato, K., Atsumi, T., Suzuki, T., Yoshitake, J., Morita, H., ... Yoshimura, T. (2007). Toll-like receptor (TLR) 2 induced through TLR4 signaling initiated by Helicobacter pylori cooperatively amplifies iNOS induction in gastric epithelial cells. American Journal of Physiology. Gastrointestinal and Liver Physiology, 293(5), pp. G1004-12.
Uno K, et al. Toll-like Receptor (TLR) 2 Induced Through TLR4 Signaling Initiated By Helicobacter Pylori Cooperatively Amplifies iNOS Induction in Gastric Epithelial Cells. Am J Physiol Gastrointest Liver Physiol. 2007;293(5):G1004-12. PubMed PMID: 17855767.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Toll-like receptor (TLR) 2 induced through TLR4 signaling initiated by Helicobacter pylori cooperatively amplifies iNOS induction in gastric epithelial cells. AU - Uno,Kaname, AU - Kato,Katsuaki, AU - Atsumi,Tomoaki, AU - Suzuki,Takehito, AU - Yoshitake,Jun, AU - Morita,Hidetoshi, AU - Ohara,Shuichi, AU - Kotake,Yashige, AU - Shimosegawa,Tooru, AU - Yoshimura,Tetsuhiko, Y1 - 2007/09/13/ PY - 2007/9/15/pubmed PY - 2007/12/28/medline PY - 2007/9/15/entrez SP - G1004 EP - 12 JF - American journal of physiology. Gastrointestinal and liver physiology JO - Am. J. Physiol. Gastrointest. Liver Physiol. VL - 293 IS - 5 N2 - Cell-surface Toll-like receptors (TLRs) initiate innate immune responses, such as inducible nitric oxide synthase (iNOS) induction, to microorganisms' surface pathogens. TLR2 and TLR4 play important roles in gastric mucosa infected with Helicobacter pylori (H. pylori), which contains lipopolysaccharide (LPS) as a pathogen. The present study investigates their physiological roles in the innate immune response of gastric epithelial cells to H. pylori-LPS. Changes in the expression of iNOS, TLR2, and TLR4, as well as downstream activation of mitogen-activated protein kinases and nuclear factor-kappaB (NF-kappaB), were analyzed in normal mouse gastric mucosal GSM06 cells following stimulation with H. pylori-LPS and interferon-gamma. Specific inhibitors for mitogen-activated protein kinases, NF-kappaB, and small interfering RNA for TLR2 or TLR4 were employed. The immunohistochemistry of TLR2 was examined in human gastric mucosa. H. pylori-LPS stimulation induced TLR2 in GSM06 cells, but TLR4 was unchanged. TLR2 induction resulted from TLR4 signaling that propagated through extracellular signal-related kinase and NF-kappaB activation, as corroborated by the decline in TLR4 expression on small interfering RNA treatment and pretreatment with inhibitors. The induction of iNOS and the associated nitric oxide production in response to H. pylori-LPS stimulation were inhibited by declines in not only TLR4 but also TLR2. Increased expression of TLR2 was identified in H. pylori-infected human gastric mucosa. TLR4 signaling initiated by H. pylori-LPS and propagated via extracellular signal-regulated kinase and NF-kappaB activation induced TLR2 expression in gastric epithelial cells. Induced TLR2 cooperated with TLR4 to amplify iNOS induction. This positive correlation may constitute a mechanism for stimulating the innate immune response against various bacterial pathogens, including H. pylori-LPS. SN - 0193-1857 UR - https://www.unboundmedicine.com/medline/citation/17855767/Toll_like_receptor__TLR__2_induced_through_TLR4_signaling_initiated_by_Helicobacter_pylori_cooperatively_amplifies_iNOS_induction_in_gastric_epithelial_cells_ L2 - http://www.physiology.org/doi/full/10.1152/ajpgi.00096.2007?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -