The Emerging Role of Interleukin-1β in Autoinflammatory Diseases

We investigated the role of nuclear factor-κB (NF-κB) in gastric ulcer healing in rats. NF-κB was activated in ulcerated tissue but not in normal mucosa, and the level of the activation was decreased with ulcer healing. NF-κB activation was observed in fibroblasts, monocytes/macrophages, and neutrophils. Treatment of gastric fibroblasts, isolated from the ulcer base, with interleukin-1β activated NF-κB and the subsequently induced cyclooxygenase-2 and cytokine-induced neutrophil chemoattractant-1 (CINC-1) mRNA expression. Inhibition of activated NF-κB action resulted in suppression of both their mRNA expression and increases in PGE2 and CINC-1 levels induced by interleukin-1β. Persistent prevention of NF-κB activation caused an impairment of ulcer healing in rats. Gene expression of interleukin-1β, CINC-1, cyclooxygenase-2, and inducible nitric oxide synthase in ulcerated tissue had been inhibited before the delay in ulcer healing became manifest. The increased levels of cyclooxygenase-2 protein and PGE2 production were also reduced. These results demonstrate that NF-κB, activated in ulcerated tissue, might upregulate the expression of healing-promoting factors responsible for gastric ulcer healing in rats.

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The Role of Arginine Vasopressin in Interleukin-1β Induced Adrenocorticotropin Secretion in the Rat

NeuroImmunoModulation ◽

10.1159/000096882 ◽

1995 ◽

Vol 2 (3) ◽

pp. 134-136 ◽

Cited By ~ 4

Author(s):

Shinsuke Sasaki ◽

Hajime Watanobe ◽

Kazuo Takebe

Keyword(s):

Arginine Vasopressin ◽

Interleukin 1Β

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Endothelial Microsomal Prostaglandin E Synthetase-1 Upregulates Vascularity and Endothelial Interleukin-1β in Deteriorative Progression of Experimental Autoimmune Encephalomyelitis

International Journal of Molecular Sciences ◽

10.3390/ijms19113647 ◽

2018 ◽

Vol 19 (11) ◽

pp. 3647 ◽

Cited By ~ 1

Author(s):

Takako Takemiya ◽

Marumi Kawakami ◽

Chisen Takeuchi

Keyword(s):

Experimental Autoimmune Encephalomyelitis ◽

Vascular Endothelial Cells ◽

Immunohistochemical Analysis ◽

Interleukin 1Β ◽

Prostaglandin E ◽

Vascular Endothelial ◽

Autoimmune Encephalomyelitis ◽

Ep Receptor ◽

Experimental Autoimmune

Microsomal prostaglandin E synthetase-1 (mPGES-1) is an inducible terminal enzyme for the production of prostaglandin E2 (PGE2). In experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, mPGES-1 is induced in vascular endothelial cells (VECs) around inflammatory foci and facilitates inflammation, demyelination, and paralysis. Therefore, we investigated the role of CD31-positive VECs in mPGES-1-mediated EAE aggravation using immunohistochemical analysis and imaging of wild-type (wt) and mPGES-1-deficient (mPGES-1−/−) mice. We demonstrated that EAE induction facilitated vascularity in inflammatory lesions in the spinal cord, and this was significantly higher in wt mice than in mPGES-1−/− mice. In addition, endothelial interleukin-1β (IL-1β) production was significantly higher in wt mice than in mPGES-1−/− mice. Moreover, endothelial PGE2 receptors (E-prostanoid (EP) receptors EP1–4) were expressed after EAE induction, and IL-1β was induced in EP receptor-positive VECs. Furthermore, IL-1 receptor 1 expression on VECs was increased upon EAE induction. Thus, increased vascularity is one mechanism involved in EAE aggravation induced by mPGES-1. Furthermore, mPGES-1 facilitated the autocrine function of VECs upon EP receptor induction and IL-1β production, modulating mPGES-1 induction in EAE.

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