Anti-inflammatory effect of MUC1 during respiratory syncytial virus infection of lung epithelial cells in vitro.
MUC1 is a transmembrane glycoprotein expressed on the apical surface of airway epithelial cells and plays an anti-inflammatory role during airway bacterial infection. In this study, we determined whether the anti-inflammatory effect of MUC1 is also operative during the respiratory syncytial virus (RSV) infection. The lung epithelial cell line A549 was treated with RSV, and the production of TNFalpha and the levels of MUC1 protein were monitored temporally during the course of infection by ELISA and Western blot analysis. Small inhibitory RNA (siRNA) transfection was utilized to assess the role of MUC1 in regulating RSV-mediated inflammatory responses by lung epithelial cells. Our results revealed that: 1) following RSV infection, an increase in MUC1 level was preceded by an increase in TNFalpha production and completely inhibited by soluble TNF receptor (TNFR); and 2) knockdown of MUC1 using MUC1 siRNA resulted in a greater increase in TNFalpha level following RSV infection compared with control siRNA treatment. We conclude that the RSV-induced increase in the TNFalpha levels upregulates MUC1 through its interaction with TNFR, which in turn suppresses further increase in TNFalpha by RSV, thus forming a negative feedback loop in the control of RSV-induced inflammation. This is the first demonstration showing that MUC1 can suppress the virus-induced inflammatory responses.
Li
Yusheng
Y
Department of Physiology and Lung Center, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
Dinwiddie
Darrell L
DL
Harrod
Kevin S
KS
Jiang
Yong
Y
Kim
K Chul
KC
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000378:metabolism*; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000378:metabolism* / Q000821:virology*; D025461:Feedback, Physiological; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D006801:Humans; D008168:Lung / Q000473:pathology* / Q000821:virology; D051379:Mice; D018396:Mucin-1 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D018357:Respiratory Syncytial Virus Infections / Q000235:genetics / Q000378:metabolism*; D012136:Respiratory Syncytial Viruses / Q000502:physiology*; D012995:Solubility; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D018396:Mucin-1; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha