p38 Mitogen-activated protein kinase regulates IL‐8 expression in human pulmonary vascular endothelial cells

Hashimoto, Shigeo; Matsumoto, Ken; Gon, Yasuhiro; Maruoka, Shuichiro; Takeshita, Ikuko; Hayashi, S.; Koura, Toshiya; Kujime, Kosei; Horie, Takashi

doi:10.1034/j.1399-3003.1999.13f21.x

Cited by 22 publications

(21 citation statements)

References 27 publications

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“…In glomerular endothelial cells, we demonstrated that LPS-induced IL-6 and IL-8 production partially depends on p38MAPK. P38MAPK dependency for LPS-induced cytokine release has been shown for several other types of endothelial cells, including human umbilical vein,25 26 human dermal microvascular,27 28 human pulmonary artery29 and rat pulmonary microvascular30 endothelial cells. Our finding that LPS-induced cytokine production by glomerular endothelial cells was only moderately blocked upon p38MAPK inhibition may be due to involvement of other kinases and transcription factors, such as phosphoinositide 3 kinase (PI3K)30 31 and nuclear factor κB 30 32 33.…”

Section: Discussionmentioning

confidence: 88%

Effects of p38 mitogen-activated protein kinase inhibition on anti-neutrophil cytoplasmic autoantibody pathogenicity in vitro and in vivo

Veen

Chen

Müller

et al. 2010

Annals of the Rheumatic Diseases

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Section: Discussionmentioning

confidence: 88%

Effects of p38 mitogen-activated protein kinase inhibition on anti-neutrophil cytoplasmic autoantibody pathogenicity in vitro and in vivo

Veen

Chen

Müller

et al. 2010

Annals of the Rheumatic Diseases

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“…In particular, the central role of p38 MAP kinase-dependent signaling in LPS-stimulated endothelium has been highlighted in recent studies (Hashimoto et al, 2000; Hippenstiel et al, 2000; Kotlyarov et al, 1999). Since Pyk2 has been implicated in the regulation of MAP kinases (Della Rocca et al, 1997; Rocic et al, 2001), we examined the role of p38 MAP kinase and p44/42 MAP kinase downstream of Pyk2 in MCP-1 production.…”

Section: Discussionmentioning

confidence: 99%

LPS-induced MCP-1 expression in human microvascular endothelial cells is mediated by the tyrosine kinase, Pyk2 via the p38 MAPK/NF-κB-dependent pathway

Anand

Bradley

Ganju

2009

Molecular Immunology

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Bacterial endotoxin (lipopolysaccharide or LPS) has potent pro-inflammatory properties and acts on many cell types including endothelial cells. Secretion of the CC chemokine, MCP-1 (CCL2) by LPSactivated endothelial cells contributes substantially to the pathogenesis of sepsis. However, the mechanism involved in LPS-induced MCP-1 production in endothelial cells is not well understood. Using human microvascular endothelial cells (HMVEC), we analyzed the involvement of the nonreceptor tyrosine kinase, Pyk2, in LPS-mediated MCP-1 production. There was a marked activation of the non-receptor tyrosine kinase, Pyk2, in response to LPS. Inhibition of Pyk2 activity using a pharmacological inhibitor, Tyrphostin A9 significantly attenuated LPS-induced Pyk2 tyrosine phosphorylation, p38 MAP kinase (MAPK) activation, NF-κB activation, and MCP-1 expression. Furthermore, specific inactivation of Pyk2 activity by transducing microvascular endothelial cells with catalytically inactive Pyk2 mutant (AAV-Pyk2MT) or Pyk2-specific siRNA significantly blocked LPS-induced MCP-1 production. The supernatants of these LPS-stimulated cells with attenuated Pyk2 activity demonstrated decreased trans-endothelial monocyte migration in comparison to LPS-treated controls, thus confirming the inhibition of functional MCP-1 production. In summary, our data suggest a critical role for the Pyk2 mediated pathway involving p38 MAP kinase and NF-κB in LPS-induced MCP-1 production in human microvascular endothelial cells.

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“…In human pulmonary vascular endothelial cells, p38 mitogen‐activated protein kinase also plays an important role in the TNF‐α‐ and IL‐1‐activated signaling pathway, which regulates interleukin‐8 expression. No evidence is available regarding its role in the cerebral vascular endothelium 23 …”

Section: Discussionmentioning

confidence: 99%

Chemokine Levels in the Jugular Venous Blood of Migraine Without Aura Patients During Attacks

Sarchielli¹,

Alberti²,

Vaianella³

et al. 2004

Headache

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The present study confirms previous findings of an increase in calcitonin gene-related peptide in internal jugular venous blood of migraine without aura patients during attacks. The transient increase in the levels of IL-8 concurs with the results of recent experimental research showing a calcitonin gene-related peptide-induced activation of IL-8 gene expression, but not RANTES and MCP-1, via the transcriptional factor AP-2, which mediates transduction in response to cyclic adenosine monophosphate. Although IL-8 is transiently increased during migraine attacks, an accumulation of leukocytes secondary to neurogenic inflammation is unlikely, as it is for other inflammatory events, because they are self limiting. Other events, including nitric oxide production, may contribute to counteract meningeal transvascular leukocyte migration during migraine attacks, as suggested by the model of sterile inflammation.

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p38 Mitogen-activated protein kinase regulates IL‐8 expression in human pulmonary vascular endothelial cells

Cited by 22 publications

References 27 publications

Effects of p38 mitogen-activated protein kinase inhibition on anti-neutrophil cytoplasmic autoantibody pathogenicity in vitro and in vivo

Effects of p38 mitogen-activated protein kinase inhibition on anti-neutrophil cytoplasmic autoantibody pathogenicity in vitro and in vivo

LPS-induced MCP-1 expression in human microvascular endothelial cells is mediated by the tyrosine kinase, Pyk2 via the p38 MAPK/NF-κB-dependent pathway

Chemokine Levels in the Jugular Venous Blood of Migraine Without Aura Patients During Attacks

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