Mite and cockroach proteases activate p44/p42 MAP kinases in human lung epithelial cells

Kuderer, Nicole M.; San‐Juan‐Vergara, Homero; Kong, Xiaoyuan; Esch, Robert E.; Lockey, Richard F.; Mohapatra, Shyam S.

doi:10.1186/1476-7961-1-1

Cited by 16 publications

(6 citation statements)

References 35 publications

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“…These cells produce many cytokines in response to dust mite molecules. These studies have shown that molecules in house dust mite extracts or specific allergens stimulate lung epithelial cells to secrete cytokines, including IL-6, IL-8, GM-CSF and eotaxin (CCL11) [29,30,31,32,33,34,35,36,37]. These same cytokines and chemokines are released by cultured fibroblasts and keratinocytes and by the cells in HSEs.…”

Section: Discussionmentioning

confidence: 99%

“…The different responses by pure cultured cells and skin equivalent tissue illustrate the danger of using cultured cells to determine the overall effect of dust mites on cells that are involved in allergic and asthmatic reactions. Many studies have stimulated lung epithelial cells in culture with house dust mite extract or recombinant house dust mite allergen [19,29,30,31,32,33,34,35]. These cells produce many cytokines in response to dust mite molecules.…”

Section: Discussionmentioning

confidence: 99%

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Immunomodulation of Skin Cytokine Secretion by House Dust Mite Extracts

Arlian

Morgan²

2011

Int Arch Allergy Immunol

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Background: Skin contact with house dust mites may contribute to atopic dermatitis and other skin diseases. We sought to determine if molecules from house dust mites could influence the release of proinflammatory cytokines and chemokines from epidermal keratinocytes and dermal fibroblasts grown in a human skin equivalent (HSE) model. Methods: HSEs consisting of an epidermis of keratinocytes with stratum corneum over a dermis of fibroblasts in a collagen matrix were challenged with Dermatophagoides farinae, D. pteronyssinus and Euroglyphus maynei mite extracts. Results: HSEs secreted interleukin (IL)-1α, IL-1 receptor antagonist, IL-6, IL-8, cutaneous T cell-attracting chemokine, transforming growth factor-α, granulocyte/macrophage and macrophage colony-stimulating factors and vascular endothelial cell growth factor in response to at least 1 mite extract. Extracts of different mite species stimulated HSEs to release different cytokines. Therefore, extracts of different species contained different molecules or different concentrations of similar molecules. The cytokine release profiles of cells in the HSEs were not the same as for monocultured keratinocytes and fibroblasts. Conclusions: Molecules from house dust mites are capable of inducing the release of multiple proinflammatory cytokines and chemokines from epidermal keratinocytes and dermal fibroblasts. Avoiding skin contact with house dust mites would reduce the possibility of mite-induced inflammation in the skin. Therefore, measures to reduce contact with mite molecules such as frequent vacuuming of upholstered furniture and carpets and laundering of clothing and bedding to remove mite molecules and allergens could reduce skin contact with mite molecules and diminish exacerbations of skin inflammation in patients with atopic dermatitis and other skin diseases.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Immunomodulation of Skin Cytokine Secretion by House Dust Mite Extracts

Arlian

Morgan²

2011

Int Arch Allergy Immunol

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“…Recently, Kuderer et al [11] reported that mite protease leads to the activation of ERK, which results in the expression of the IL-8 gene in human lung epithelial cells. We extended their study by examining the transduction pathways induced by HDM stimuli for IL-8 production in more detail.…”

Section: Discussionmentioning

confidence: 99%

“…Stacey et al [10] reported that nuclear factor ĸB activation plays a dominant role in Der p 1-induced chemokine production. Additionally, Kuderer et al [11] showed that extracellular signal-regulated kinase (ERK) may play an important role in D. farinae -induced IL-8 production. Thus, we examined the roles of various signaling molecules activated by D. farinae .…”

Section: Introductionmentioning

confidence: 99%

Calcium-Calmodulin Mediates House Dust Mite-Induced ERK Activation and IL-8 Production in Human Respiratory Epithelial Cells

Sohn

Lee²,

Kim³

et al. 2007

Respiration

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Background:House dust mites (HDM) have been shown to be important sources of indoor allergens associated with asthma and other allergic conditions. While exogenous proteases from allergens have a direct proinflammatory role in the respiratory tract, the precise mechanisms underlying the release of cytokines from the respiratory epithelium are unclear. Objectives: The present study examines that extracellular signal-regulated kinase (ERK) activated downstream of the Ca²⁺-sensitive tyrosine kinase plays an important role in the efficient activation of the HDM-induced IL-8 signaling pathway. Methods: We examined the effect of HDM, and the role of the Ca²⁺/calmodulin system and mitogen-activated protein kinases, on IL-8 expression in human lung epithelial cells. Results: In H292 cells, HDM induced IL-8 release in a time- and/or dose-dependent manner. This IL-8 release was abolished by treatment with intracellular Ca²⁺ chelator (BAPTA-AM), but not by EGTA or nifedipine. Calmodulin inhibitor (calmidazolium) and tyrosine kinase inhibitor (genistein) almost completely blocked IL-8 release by HDM. PD98059, an ERK pathway inhibitor, completely abolished HDM-induced IL-8 release. Moreover, PD98059, BAPTA-AM, calmidazolium and genistein suppressed the HDM-induced ERK phosphorylation. Conclusions: HDM-induced IL-8 production is predominantly regulated by Ca²⁺/calmodulin signaling, and ERK plays an important role in signal transmission for efficient activation of the HDM-induced IL-8 signaling pathway.

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“…Typically, PAR-2 is cleaved and activated by serine proteases, such as trypsin [18,19] and the house dust mite allergens Der p 3 and Der p 9 [20]. On the other hand, in a human epithelial cell line stimulated with German cockroach extract, the aspartate protease inhibitor pepstatin A and the cysteine protease inhibitor E64, inhibited phospho-p44 MAP kinase levels [44], suggesting a role for cysteine proteases or aspartate proteases. Our study of eosinophils [22] supports and extends the findings of earlier studies that demonstrated German cockroach extract activation of PAR-2 in human airway epithelial cells [15,45], mouse lung fibroblasts [46], and human keratinocytes [40].…”

Section: Epithelial Cellsmentioning

confidence: 99%

Cockroach Induces Inflammatory Responses through Protease-Dependent Pathways

Wada

Matsuwaki

Moriyama

et al. 2011

Int Arch Allergy Immunol

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Exposure to cockroaches is a major risk factor for asthma. Products from cockroaches may contain proteases and ligands for pattern recognition receptors. These molecules may activate airway inflammatory cells, such as eosinophils, that are involved in asthma. Among inner-city children, cockroach allergens play an especially important role in increasing asthma morbidity. The molecular mechanism for this association between cockroach exposure and asthma is not fully understood. Enzymatic activities from cockroaches activate inflammatory cells in the airways and may also exacerbate certain human airway diseases, such as asthma. We recently reported that cockroach extracts contain pepstatin A-sensitive proteases that activate PAR-2 and induce activation and degranulation of human eosinophils. This review focuses on the effects of cockroach on various inflammatory cells, including eosinophils, epithelial cells, fibroblasts, dendritic cells, and T cells, in allergic reactions.

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Mite and cockroach proteases activate p44/p42 MAP kinases in human lung epithelial cells

Abstract: Background: The mechanisms underlying epithelial cell activation by indoor inhaled antigens are poorly understood.

Cited by 16 publications

References 35 publications

Immunomodulation of Skin Cytokine Secretion by House Dust Mite Extracts

Immunomodulation of Skin Cytokine Secretion by House Dust Mite Extracts

Calcium-Calmodulin Mediates House Dust Mite-Induced ERK Activation and IL-8 Production in Human Respiratory Epithelial Cells

Cockroach Induces Inflammatory Responses through Protease-Dependent Pathways

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