Effects Of Calcium-binding Protein S100A8/A9 On The Pathogenesis Of Chronic Obstructive Pulmonary Disease

Objective: To explore the role of S100A8/A9 in the pathogenesis of chronic obstructive pulmonary disease(COPD), we investigated the change of plasma and induced sputum S100A8/A9 concentration, as well as plasma interleukin-1β(IL-1β),interleukin-8(IL-8),interleukin-12p70(IL-12p70) and tumor necrosis factor-ɑ(TNF-ɑ) level of AECOPD,stable COPD patients and healthy control. We also observed the expression of S100A8, S100A9 m RNA and S100A8/A9 protein in the lung tissue of peoples suffering from COPD or the control.Method:(1) Collected outpatient or inpatient COPD patients and physical examination peoples in North sichuan medical college affiliated hospital from August 2013 to January 2014. They were divided into AECOPD group, stable COPD group and healthy control group. Each group consisted of 30 cases. Used double antibody sandwich ELISA to detect the plasma concentrations of S100A8/A9, IL-1β, IL-8, IL-12p70, TNF-ɑ and induced sputum concentration of S100A8/A9.(2) Collected the lung tissue samples from lung cancer surgery patients from May 2013 to January 2014 in North Sichuan Medical College Hospital, which were away from cancer tissue above 5cm. These subjects were divided into COPD group(20 cases) and control group(28 cases). Used the reverse transcription- polymerase chain reaction(RT-PCR) method for the determination S100A8, S100A9 m RNA levels in the lung tissue of two groups of patients. The S100A8/A9 protein expression in the lung tissue was observed by using immunohistochemistry.Results:(1) The plasma and induced sputum S100A8/A9 levels, plasma IL-1β, IL-8, TNF-ɑ concentrations in the AECOPD and stable COPD group were significantly higher than those in the healthy control group(P <0.01), and the plasma and induced sputum S100A8/A9 levels, plasma IL-1β, IL-8, TNF-ɑ concentrations in the AECOPD group were significantly increased compared with stable COPD group(P <0.01).(2) The plasma concentrations of IL-12p70 in AECOPD and stable COPD group were significantly lower than those in the healthy control group(P <0.01), while the concentration of plasma IL-12p70 in the AECOPD group was significantly lower than that in the stable COPD group(P <0.01).(3) The expression of S100A8, S100A9 m RNA in lung tissue of patients with the COPD group were significantly higher than those of patients with the control group(P <0.01).(4) The expression of S100A8/A9 protein in lung tissue of patients with the COPD group was significantly higher than that of patients with the control group(P <0.01).Conclusion:(1) The synthesis and release of S100A8/A9, IL-1β, IL-8, and TNF-ɑ in the patients with COPD are significantly increased, and the synthesis and release of IL-12p70 in COPD patients is significantly reduced.(2) The concentrations of S100A8/A9 in plasma and induced sputum, and the concentrations of IL-1β, IL-8 and TNF-α in plasma of COPD patients are positively related to the severity of airflow limitation, and IL-12p70 concentration in plasma of patients with COPD correlated negatively with the severity of airflow limitation.(3) The expression of S100A8, S100A9 m RNA and S100A8/A9 protein in lung tissue of COPD patients is increased; The expression levels of S100A8, S100A9 m RNA and S100A8/A9 protein in lung tissue of COPD patients are positively correlated with airflow limitation severity.(4) S100A8/A9 plays an important role in the pathogenesis of COPD, it may be mainly involved in inflammation mechanism.