Oral corticosteroids decrease eosinophil and CC chemokine expression but increase neutrophil, IL-8, and IFN-γ–inducible protein 10 expression in asthmatic airway mucosa

Fukakusa, Motonori; Bergeron, C.; Tulic, Meri K.; Fiset, Pierre‐Olivier; Dewachi, Oday; Laviolette, Michel; Hamid, Qutayba; Chakir, Jamila

doi:10.1016/j.jaci.2004.10.036

Cited by 112 publications

(94 citation statements)

References 24 publications

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“…One explanation might be that steroids differentially regulate neutrophil and eosinophil cytokines. In asthma, it has been reported that corticosteroids downregulate the number of eosinophils and the level of CC chemokines in bronchial lavage, whereas neither the number of neutrophils nor IL-8 levels were affected (26). The mechanisms involved are currently unknown.…”

Section: Discussionmentioning

confidence: 99%

Immunomodulation of Nasal Epithelial Cells by Staphylococcus aureus-Derived Serine Proteases

Rudack

Sachse²,

Albert³

et al. 2009

The Journal of Immunology

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The impact of Staphylococcus aureus in the pathogenesis of chronic rhinosinusitis is not well understood. Therefore, we investigated primary human nasal epithelial cell cultures for their ability to produce IL-8, growth-related oncogene-α, and IL-6 via stimulation with trypsin and culture supernatants of different S. aureus strains and phenotypes. Inhibition of cytokine synthesis was performed using a glucocorticoid, a serine protease inhibitor, and a cysteine protease inhibitor. Finally, signal transduction pathways were analyzed by quantifying phosphorylated forms of MAPKs (PI3K, ERK, and p38) and DNA-binding assays that quantified NF-κB and its inhibition using BAY11-7085. In vitro studies showed that the induction of IL-8, growth-related oncogene-α, and IL-6 by S. aureus culture supernatants was significantly inhibited by the serine protease inhibitor. In contrast, steroids and the cysteine protease inhibitor had little effect. Activation of NF-κB was observed after cell treatment with trypsin and bacterial supernatants, and was inhibited by BAY11-7085 and the serine protease inhibitor. S. aureus serine proteases were identified to modulate chemokine synthesis and activate NF-κB in nasal epithelial cells, and may therefore be relevant for the pathophysiology of chronic rhinosinusitis.

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Section: Discussionmentioning

confidence: 99%

Immunomodulation of Nasal Epithelial Cells by Staphylococcus aureus-Derived Serine Proteases

Rudack

Sachse²,

Albert³

et al. 2009

The Journal of Immunology

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“…It has been shown in a murine model that blockage of CCL2 reduced both lung leukocyte infiltration and bronchial hyperreactivity (41). In addition, a recent study showed that corticosteroids had no effects on CCL2 mRNA expression in bronchial epithelium and submucosa in asthmatic patients, suggesting that a part of this inflammatory pathway related to cysLTs may not be fully inhibited by corticosteroid treatment (42). Similarly, among chemokines involved in the pathogenesis of atherosclerosis, CCL2 seems to play one of the major roles (43).…”

Section: Discussionmentioning

confidence: 99%

Functional Characterization of Human Cysteinyl Leukotriene 1 Receptor Gene Structure

Woszczek

Pawliczak

et al. 2005

The Journal of Immunology

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The 5-lipoxygenase pathway has been strongly implicated in the pathogenesis of chronic inflammatory disorders, such as bronchial asthma and atherosclerosis. Cysteinyl leukotrienes (cysLTs), 5-lipoxygenase pathway products, are recognized now not only as important factors in asthmatic inflammation, but also as mediators of cell trafficking and innate immune responses. To study a role of cysLTs in inflammatory reactions we have characterized the gene structure of human cysteinyl leukotriene receptor type I (cysLT1R). The cysLT1R gene consists of 5 exons that are variably spliced and a single promoter region with multiple transcription start sites. Four different cysLT1R transcripts were identified. RT-PCR showed dominant and wide expression of the transcript I, containing exons 1, 4, and 5, with the strongest presence in blood leukocytes, spleen, thymus, lung, and heart. The expression of cysLT1R is functionally regulated at the transcriptional level by IL-4 through a STAT6 response element localized to the proximal cysLT1R promoter region. IL-4 stimulation increased cysLT1R mRNA (real-time PCR) and surface protein expression (flow cytometry) in a time-dependent fashion. CysLTs (LTD4 and LTC4) induced an increased production of a potent monocyte chemoattractant CCL2 (MCP-1) in IL-4-primed THP-1 cells in a dose-dependent manner. This effect was effectively inhibited by the cysLT1R-selective antagonist MK571 in a dose-dependent manner and only partially by a nonselective cysLT1R/cysLT2R inhibitor BAY-u9773, implying a cysLT1R-mediated mechanism. Thus, cysLTs signaling through cysLT1R might contribute to inflammatory reactions by cooperating with IL-4 in enhanced CCL2 production in human monocytic cells.

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“…Prednisolone treatment is known to decrease AHR, eosinophilia in the lung, serum IgE levels, and IL-2 and IL-4 production by ConA-stimulated splenocytes [38, 39]. However, the side effects of corticosteroids may cause problems.…”

Section: Discussionmentioning

confidence: 99%

Effects of Triterpenoid-Rich Extracts of <i>Ganoderma tsugae</i> on Airway Hyperreactivity and Th2 Responses in vivo

Chen¹,

Lin²

2006

Int Arch Allergy Immunol

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Background: Airway inflammation and Th2 responses play central roles in allergic asthma. We have previously reported that Ganoderma tsugae supplementation could attenuate airway inflammation in the murine model. Since it remains unclear which part of the G. tsugae exerts this effect on allergic asthma in vivo, this study was meant to investigate if triterpenoid extracts have anti-inflammatory effects on airway responses and regulatory effects on Th2 responses. Methods: BALB/c mice sensitized intraperitoneally and challenged with ovalbumin (OVA) were treated with either triterpenoid-rich extracts (TRE) of G. tsugae or prednisolone for 2 weeks. The effects of TRE on bronchial airway hyperresponsiveness (AHR), airway inflammation, serum antigen-specific antibody levels, and cytokine secretions from splenocytes were evaluated. Results: TRE supplementation significantly decreased AHR and reduced the total infiltrating leukocytes and eosinophils, as well as the levels of inflammatory mediators, such as interleukin (IL)-4, IL-5 and eotaxin in bronchoalveolar lavage fluid when compared with those of the control group. Lung histology also showed less cell recruitment and lung damage. TRE supplements suppressed IL-5 secretions from OVA-stimulated splenocytes, but did not affect the cell number of splenocytes, which was also reduced by prednisolone. Although OVA-specific immunoglobulin E levels were not significantly different among the groups, a lower level of OVA-specific immunoglobulin G1, another Th2-related antibody, was found in TRE and prednisolone treatment. Conclusions: TRE of G. tsugae exert anti-inflammatory effects on airway responses and attenuate Th2 responses without the overall immunosuppression effects in allergic murine models of asthma.

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Oral corticosteroids decrease eosinophil and CC chemokine expression but increase neutrophil, IL-8, and IFN-γ–inducible protein 10 expression in asthmatic airway mucosa

Cited by 112 publications

References 24 publications

Immunomodulation of Nasal Epithelial Cells by Staphylococcus aureus-Derived Serine Proteases

Immunomodulation of Nasal Epithelial Cells by Staphylococcus aureus-Derived Serine Proteases

Functional Characterization of Human Cysteinyl Leukotriene 1 Receptor Gene Structure

Effects of Triterpenoid-Rich Extracts of <i>Ganoderma tsugae</i> on Airway Hyperreactivity and Th2 Responses in vivo

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