Human neutrophil peptides induce interleukin-8 production through the P2Y6 signaling pathway

Khine, Aye Aye; Sorbo, Lorenzo Del; Vaschetto, Rosanna; Voglis, Stefanos; Tullis, Elizabeth; Slutsky, Arthur S.; Downey, Gregory P.; Zhang, Haibo

doi:10.1182/blood-2005-06-2314

Cited by 106 publications

(118 citation statements)

References 46 publications

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“…6 in the HNP-1-induced suppression of neutrophil apoptosis. Although P2Y 6 is known as a purinergic receptor for UDP (30), it has been reported that HNPs utilize the P2Y 6 signaling pathway to stimulate human lung epithelial cells to produce IL-8 (28). Thus, we determined the involvement of P2Y 6 in the HNP-1-induced suppression of neutrophil apoptosis.…”

Section: Effects Of Hnp-1 On the Expression Of Truncated Bid Andmentioning

confidence: 97%

“…For instance, human cathelicidin LL-37 activates neutrophils, monocytes and T cells via the interactions with FPRL1, a low-affinity formyl-peptide receptor (24,26) and P2X 7 , a nucleotide receptor (26,45,46). In addition, HNPs induce IL-8 production from lung epithelial cells via the P2Y 6 signaling pathway (28), and hBD-2 chemoattracts immature dendritic cells and T cells and TNF-·-primed neutrophils via the action on CCR6 (23,25). Moreover, we have previously revealed that hBD-3 induces the suppression of neutrophil apoptosis by acting on CCR6 (27).…”

Section: Discussionmentioning

confidence: 99%

“…3 and 5). In addition, we evaluated the involvement of the P2Y 6 nucleotide receptor in the HNP-1-induced suppression of neutrophil apoptosis by using a selective P2Y 6 antagonist (MRS2578) (31), since it has been demonstrated that HNPs utilize the P2Y 6 signaling pathway to stimulate human lung epithelial cells to produce IL-8 (28), and that human neutrophils express the P2Y 6 receptor (29). RT-PCR and Western blot analyses indicated that neutrophils express the P2Y 6 receptor ( Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Based on these findings, we previously evaluated the potential effects of LL-37 and hBDs on neutrophil apoptosis, and revealed that LL-37 and hBD-3 suppress neutrophil apoptosis via the actions on a low affinity formyl-peptide receptor, formylpeptide receptor-like 1 (FPRL1), and the nucleotide receptor, P2X 7 (26), as well as the CC chemokine receptor (CCR)-6 (27), respectively. Of importance, it has been demonstrated that HNPs utilize the P2Y 6 signaling pathway to stimulate human lung epithelial cells to produce IL-8 (28), and that human neutrophils express the P2Y 6 receptor (29). Thus, we hypothesized that HNPs could also have a potential to activate neutrophils to modulate apoptosis via the action on P2Y 6 .…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of the effect of α-defensin human neutrophil peptides on neutrophil apoptosis

Nagaoka

Suzuki²,

Murakami³

et al. 2010

Int J Mol Med

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Section: Effects Of Hnp-1 On the Expression Of Truncated Bid Andmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Evaluation of the effect of α-defensin human neutrophil peptides on neutrophil apoptosis

Nagaoka

Suzuki²,

Murakami³

et al. 2010

Int J Mol Med

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“…In accordance with the notion that defensins are capable of inducing the maturation/activation of antigen-presenting cells, enhanced antigen-specific humoral and cellular immune responses were found when antigen was administered in combination with HNP or mouse-homologues of beta-defensins [12,26]. Furthermore, defensins were demonstrated to inhibit the classic and lectin pathway of complement activation by binding C1q and mannose-binding lectin [29,30], they increase proliferation, migration, and proinflammatory cytokine secretion in keratinocytes [31][32][33], and enhance antigen-presentation and proinflammatory cytokine secretion in lung epithelial cells [27,[34][35][36]. enhancing antigen-specific humoral and cellular immune response HNP [12,26] Legend Our current understanding of inciting events in autoimmune disorders such as systemic lupus erythematosus or rheumatoid arthritis crucially involves presentation of autoantigens by antigen-presenting cells to T-cells which subsequently promote adaptive immune responses including the generation of autoantibodies.…”

Section: Immunomodulatory Effect Of Defensinsmentioning

confidence: 99%

Defensins: Potential Effectors in Autoimmune Rheumatic Disorders

Vordenbäumen

Schneider

2011

Polymers

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Abstract:Defensins are small cationic peptides with antimicrobial properties. They constitute a highly conserved innate immune defense mechanism across species. Based on the arrangement of disulfide-bonds, α-and β-defensins are distinguished in humans. Both types of defensin comprise several distinct molecules that are preferentially expressed at epithelial surfaces and in blood cells. In the last decade, multiple immunomodulatory functions of defensins have been recognized, including chemotactic activity, the promotion of antigen presentation, and modulations of proinflammatory cytokine secretion. These findings suggested a role for defensins not only as a first line of defense, but also as connectors of innate and adaptive immune responses. Recently, increasingly accumulating evidence has indicated that defensins may also be involved in the pathogenesis of autoimmune rheumatic disorders such as systemic lupus erythematosus and rheumatoid arthritis. The current review summarizes the data connecting defensins to autoimmunity.

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Differential signaling mechanisms of HNP‐induced IL‐8 production in human lung epithelial cells and monocytes

Syeda

Liu

Tullis

et al. 2007

Journal Cellular Physiology

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Human neutrophil peptides (HNP) kill microorganisms but also modulate immune responses through upregulation of the chemokine IL-8 by activation of the nucleotide P2Y 6 receptor. However, the intracellular signaling mechanisms remain yet to be determined. Human lung epithelial cells (A549) and monocytes (U937) were stimulated with HNP in the absence and presence of the specific kinase inhibitors for Src, ERK1/2, p38 MAPK, JNK and Akt. HNP induced a rapid phosphorylation of the kinases in both cell types associated with a dosedependent, selective production of IL-8 among ten cytokines assayed. The HNP-induced IL-8 production was blocked by the Src tyrosine kinase inhibitor PP2, MEK1/2 inhibitor U0126 and the PI3K inhibitor LY294002, but not by the JNK inhibitor SP600125 in both cell types. Treatment with the p38 inhibitor SB203580 attenuated the HNP-induced IL-8 production only in monocytes. Blockade of Src kinase blunted HNP-induced phosphorylation of the ERK1/2 and Akt but not p38 in monocytes. In contrast, Src inhibition had no effect on phosphorylation of the other kinases in the lung epithelial cells. We conclude that the activation of ERK1/2 and PI3K/Akt pathways is required for HNP-induced IL-8 release which occurs in a Src-independent manner in lung epithelial cells, while is Src-dependent in monocytes.

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Human neutrophil peptides induce interleukin-8 production through the P2Y6 signaling pathway

Cited by 106 publications

References 46 publications

Evaluation of the effect of α-defensin human neutrophil peptides on neutrophil apoptosis

Evaluation of the effect of α-defensin human neutrophil peptides on neutrophil apoptosis

Defensins: Potential Effectors in Autoimmune Rheumatic Disorders

Differential signaling mechanisms of HNP‐induced IL‐8 production in human lung epithelial cells and monocytes

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