Role of Interleukin-32 in Helicobacter pylori-Induced Gastric Inflammation

Sakitani, Kosuke; Hirata, Yoshihiro; Hayakawa, Yoku; Serizawa, Takako; Nakata, Wachiko; Takahashi, Ryōsuke; Kinoshita, Hiroto; Sakamoto, Kei; Nakagawa, Hayato; Akanuma, Masao; Yoshida, Haruhiko; Maeda, Shin; Koike, Kazuhiko

doi:10.1128/iai.00637-12

Cited by 52 publications

(48 citation statements)

References 54 publications

(59 reference statements)

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“…The increase of IL-32 expression in E. coli-infected cells or in the udder tissue of E. coli-infected cows was consistent with other studies of IL-32 in response to Gram-negative pathogens and endotoxin (35)(36)(37). In contrast, expression of IL-32 by S. aureusinfected cells was decreased.…”

Section: Discussionsupporting

confidence: 79%

Staphylococcus aureus Phenol-Soluble Modulins Impair Interleukin Expression in Bovine Mammary Epithelial Cells

et al. 2016

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iThe role of the recently described interleukin-32 (IL-32) in Staphylococcus aureus-induced mastitis, an inflammation of the mammary gland, is unclear. We determined expression of IL-32, IL-6, and IL-8 in S. aureus-and Escherichia coli-infected bovine mammary gland epithelial cells. Using live bacteria, we found that in S. aureus-infected cells, induction of IL-6 and IL-8 expression was less pronounced than in E. coli-infected cells. Notably, IL-32 expression was decreased in S. aureus-infected cells, while it was increased in E. coli-infected cells. We identified the staphylococcal phenol-soluble modulin (PSM) peptides as key contributors to these effects, as IL-32, IL-6, and IL-8 expression by epithelial cells exposed to psm mutant strains was significantly increased compared to that in cells exposed to the isogenic S. aureus wild-type strain, indicating that PSMs inhibit the production of these interleukins. The use of genetically complemented strains confirmed this observation. Inasmuch as the decreased expression of IL-32, which is involved in dendritic cell maturation, impairs immune responses, our results support a PSM-dependent mechanism that allows for the development of chronic S. aureus-related mastitis.

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Section: Discussionsupporting

confidence: 79%

Staphylococcus aureus Phenol-Soluble Modulins Impair Interleukin Expression in Bovine Mammary Epithelial Cells

et al. 2016

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“…It has been reported that H. pylori and its virulence factor cag pathogenicity island (PAI) activates nuclear factor-B (NF-B) and MAPK signaling through MyD88 and TAK1 activation (15)(16)(17)(18)(19)(20). The activation of these signaling pathways is important for the cytokine production or cell proliferation that leads to the development of gastric cancer (21)(22)(23)(24). However, the relationship between H. pylori and ASK1 in epithelial cells has not been fully investigated.…”

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confidence: 99%

Differential Roles of ASK1 and TAK1 in Helicobacter pylori-Induced Cellular Responses

et al. 2013

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The mitogen-activated protein kinase (MAPK) signaling pathway regulates various cellular functions, including those induced by Helicobacter pylori. TAK1 is an upstream MAPK kinase kinase (MAP3K) required for H. pylori-induced MAPK and NF-B activation, but it remains unclear whether other MAP3Ks are involved in H. pylori-induced cellular responses. In this study, we focused on the MAP3K ASK1, which plays a critical role in gastric tumorigenesis. In gastric epithelial cells, H. pylori activates ASK1 in a reactive oxygen species (ROS)-and cag pathogenicity island-dependent manner, and ASK1 regulates sustained JNK activation and apoptosis induced by H. pylori. In contrast, TAK1 regulates H. pylori-mediated early JNK activation and cytokine production. We also found reciprocal regulation between ASK1 and TAK1 in H. pylori-related responses, whereby inhibition of TAK1 or downstream p38 MAPK activates ASK1 through ROS production, and ASK1 suppresses TAK1 and downstream NF-B activation. We identified ROS/ASK1/JNK as a new signaling pathway induced by H. pylori, which regulates apoptotic cell death. The balance of ASK1-induced apoptosis and TAK1-induced antiapoptotic or inflammatory responses may determine the fate of epithelial cells infected with H. pylori and thus be involved in the pathogenesis of gastritis and gastric cancer.T he mitogen-activated protein kinase (MAPK) signaling pathway is involved in various cellular functions, including cell cycle, apoptosis, inflammatory responses, and differentiation (1). This pathway consists of three sequential kinases, MAPK kinase kinase (MAP3K), MAPK kinase (MAP2K), and MAPK. More than 20 kinds of MAP3Ks regulate different and distinct functions depending on the stimuli or stresses involved (2).Apoptosis signal-regulating kinase 1 (ASK1) is a MAP3K that regulates apoptosis, immune responses, and carcinogenesis (3-5). ASK1 binds directly to thioredoxin (TRX), a reduction/oxidation regulatory protein, and intracellular reactive oxygen species (ROS) can activate ASK1 by dissociating it from TRX (6). ASK1 activates the downstream MAPKs c-Jun-N-terminal kinase (JNK) and p38 through phosphorylation of the MAP2Ks, MKK4, and MKK3. ASK1 and subsequent MAPK activation are involved in various human diseases (7, 8), and we reported previously that ASK1 plays critical roles in the development of colitis, colon cancer, liver injury, liver cancer, and gastric cancer (9-13).Gastric cancer is one of the most common cancers worldwide, and Helicobacter pylori is known to be a critical risk factor for the disease (14). It has been reported that H. pylori and its virulence factor cag pathogenicity island (PAI) activates nuclear factor-B (NF-B) and MAPK signaling through MyD88 and TAK1 activation (15)(16)(17)(18)(19)(20). The activation of these signaling pathways is important for the cytokine production or cell proliferation that leads to the development of gastric cancer (21-24). However, the relationship between H. pylori and ASK1 in epithelial cells has not been fully investigated.TAK1 positi...

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“…In stomach cancer, this cytokine is involved in process of carcinogenesis since beginning. That was proved in patients with confirmed Helicobacter pylori inflammation, which is confirmed carcinogen (72,73). Their gastric mucosa expresses higher levels of IL-32, as well as levels in sera of same patients.…”

Section: Role In Cancer Biologymentioning

confidence: 82%