(Chest. 2003;123:425S.)
© 2003
American College of Chest Physicians
Mycoplasma pneumoniae Antigens Stimulate Interleukin-8*
Kathryn Chmura, BA;
Ryan D. Lutz, BS;
Hirofumi Chiba, MD, PhD;
Mari S. Numata, MD, PhD;
Hee-Jung Choi, MD, PhD;
Giamila Fantuzzi, PhD;
Dennis R. Voelker, PhD and
Edward D. Chan, MD
* From the Department of Medicine (Ms. Chmura, Mr. Lutz, Drs. Chiba, and Numata) and Program in Cell Biology (Dr. Voelker), National Jewish Medical and Research Center; and the Divisions of Pulmonary Sciences and Critical Care Medicine (Dr. Chan) and Infectious Diseases (Dr. Choi and Fantuzzi), University of Colorado Health Sciences Center, Denver, CO.
Correspondence to: Edward D. Chan, MD, K613e, Goodman Building, National Jewish Medical and Research Center, 1400 Jackson St, Denver, CO 80206; e-mail: chane{at}njc.org
Asthma is characterized by the presence of airway inflammation that results in bronchial hyperresponsiveness and symptoms of airway obstruction. Persistent and severe asthma may have an eosinophilic or noneosinophilic infiltration of the airways, the latter characterized by a profusion of neutrophils.1
More recent findings implicate that neutrophils may play a role in the irreversible airflow limitation seen in asthma.2
3
There is evidence that some chronic asthmatics have an increased incidence of polymerase chain reaction positivity for Mycoplasma pneumoniae and that these patients may have a clinical response to clarithromycin therapy.4
In an animal model of asthma in which BALB/c mice were inoculated intranasally with M pneumoniae, bronchial hyperresponsiveness developed.5
In addition, the resultant inflammation was principally neutrophilic.
Since epithelial cells are important in the recruitment of inflammatory cells into the airways, we sought to investigate whether mycoplasma antigens could induce interleukin (IL)-8, a potent chemokine for neutrophils. Cultured BEAS-2B human bronchial epithelial cells stimulated with mycoplasma membrane fraction (MMF) increased IL-8 production in a dose-dependent fashion (Fig 1
). Stimulation of the BEAS-2B cells with 10 ng/mL of lipopolysaccharide or with MMF plus 10 µmol/L polymyxin B demonstrated that the ability of MMF to induce IL-8 was not due to contaminating lipopolysaccharide (data not shown). In addition, MMF activated nuclear factor-
B, a transcription factor known to bind to a B cis-element on the 5'-flanking region of the IL-8 promoter. Inhibition of nuclear factor-B activation with an IB
-kinase inhibitor (BAY11–7082) resulted in significant inhibition of MMF-induced IL-8 protein expression. MMF also activated all three isoforms of the mitogen-activated protein kinases. Co-culture of MMF-stimulated BEAS-2B cells with inhibitors of the mitogen-activated protein kinase pathways revealed that these serine-threonine kinases modulate MMF-induced IL-8 expression in a complex fashion. In conclusion, these findings show that mycoplasma antigens are able to induce IL-8 production in human airway epithelial cells. We hypothesize that infection with these organisms may play a role in the pathogenesis of the neutrophilic response that characterizes many cases of severe asthma.
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Figure 1.. MMF induces IL-8 expression in BEAS-2B cells. Cultured BEAS-2B cells were stimulated with the indicated concentrations of MMF for 48 h, and the cultured supernatant were assayed for IL-8 by electrochemiluminescence.
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Footnotes
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Abbreviations: IL = interleukin; MMF = mycoplasma membrane fraction
Dr. Chan is supported by National Institutes of Health grant HL66112, the Parke-Davis Atorvastatin Research Award, and the American Lung Association Career Investigator Award.
Dr. Voelker is supported by National Institutes of Health grant HL45286.
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References
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- Wenzel, SE, Szefler, SJ, Leung, DY, et al (1997) Bronchoscopic evaluation of severe asthma: persistent inflammation associated with high dose glucocorticoids. Am J Respir Crit Care Med 156,737-743[Abstract/Free Full Text]
- Little, SA, MacLeod, KJ, Chalmers, GW, et al Association of forced expiratory volume with disease duration and sputum neutrophils in chronic asthma. Am J Med 2002;112,446-452[CrossRef][ISI][Medline]
- Woodruff, PG, Fahy, JV A role for neutrophils in asthma? Am J Med 2002;112,498-500[CrossRef][ISI][Medline]
- Kraft, M, Cassell, GH, Henson, JE, et al Detection of Mycoplasma pneumoniae in the airways of adults with chronic asthma. Am J Respir Crit Care Med 1998;158,998-1001[Abstract/Free Full Text]
- Martin, RJ, Chu, HW, Honour, JM, et al Airway inflammation and bronchial hyperresponsiveness after Mycoplasma pneumoniae infection in a murine model. Am J Respir Cell Mol Biol 2001;24,577-582[Abstract/Free Full Text]
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