Monocyte‐derived fibrocytes induce an inflammatory phenotype in airway smooth muscle cells. Issue 11 (November 2014)

• Record Type: Journal Article
• Authors: Lin, T.‐Y.; Venkatesan, N.; Nishioka, M.; Kyoh, S.; Al‐Alwan, L.; Baglole, C. J.; Eidelman, D. H.; Ludwig, M. S.; Hamid, Q.
• Is Part Of: Clinical & experimental allergy. Volume 44:Issue 11(2014:Nov.)
• Page Start: 1347
• Page End: 1360
• Publication Date: 2014-11
• Subjects: Allergy -- Periodicals; Immunology -- Periodicals; 616.97
• DOI: 10.1111/cea.12421
• Languages: English
• ISSNs: 0954-7894

Abstract

<abstract abstract-type="main" id="cea12421-abs-0001"> <title>Summary</title> <sec id="cea12421-sec-0001" sec-type="section"> <title>Background</title> <p>Infiltration of fibrocytes (FC) in the airway smooth muscle is a feature of asthma, but the pathological significance is unknown.</p> </sec> <sec id="cea12421-sec-0002" sec-type="section"> <title>Objective</title> <p>We sought to explore whether FC modulate the phenotype of airway smooth muscle cells (ASMC) in asthmatic vs. control subjects.</p> </sec> <sec id="cea12421-sec-0003" sec-type="section"> <title>Methods</title> <p>Fibrocytes were isolated from CD14+ monocytes from asthmatic and normal subjects. Proliferation of ASMC of asthmatic or normal subjects was analysed by <sup>3</sup>H‐thymidine incorporation, cell number counting and Ki‐67 expression after treatment of ASMC with FC‐conditioned medium (FCCM) or co‐culture with FC. ASMC‐associated cytokines/chemokines implicated in asthma (TGF‐β1, eotaxin, IL‐6 and IL‐8) were measured in co‐culture or transwell culture of ASMC + FC by ELISA. Immunofluorescence staining was performed to localize these cytokines in ASMC. Cytokine secretion was measured in the transwell culture of ASMC + FC, where NF‐κB‐p65 or ERK1/2 in ASMC was silenced by siRNA. Contractile phenotype of ASMC in transwell culture was assessed by immunoblotting of α‐smooth muscle actin (α‐SMA) and myosin light chain kinase (MLCK).</p> </sec> <sec id="cea12421-sec-0004" sec-type="section"> <title>Results</title> <p>Fibrocytes did not affect ASMC proliferation and expression of TGF‐β1, eotaxin, α‐SMA and MLCK; however, ASMC production of IL‐8 and IL‐6 was increased in the co‐culture and transwell culture by FC. ASMC treated with FCCM were immunopositive for IL‐8/IL‐6 and produced more IL‐8/IL‐6. Furthermore, siRNA silencing of NF‐κB‐p65 or ERK1/2 in transwell cultures of asthmatic ASMC with normal subject FC decreased IL‐8 and IL‐6 production.</p> </sec> <sec id="cea12421-sec-0005" sec-type="section"> <title>Conclusions and Clinical Relevance</title> <p>Fibrocytes promoted IL‐8 and IL‐6 production by ASMC, demonstrating a proinflammatory role for FC and a possible mechanism of the inflammatory phenotype in asthma.</p> </sec> </abstract>