Changes And Significance Of Chemokines Ip-10and Tarc In Lungs Of Experimental Silicotic Rats

Background: Silicosis, also known as Potter’s rot, is a type of pneumoconiosis.Silicosis is the most common occupational lung disease worldwide, especially indeveloping countries. It not only endangers the health of workers, reduces their abilityto work and their quality of life, but will eventually cause huge economic losses tocountries. At present, China is still the most seriously affected country. Not only theexisting number of people suffering from silicosis, but also the number of new casesand the number of people exposed to silica dust in China are the largest in the world.Therefore, research on prevention of silicosis has become more and more important. Asa relatively safe technology, Bronchoalveolar Lavage（BAL）has been widely used forboth research and diagnostic indications by analyzing the cellular components ofBronchoalveolar Lavage Fluid （BALF）. In recent years, the imbalance of Th1and Th2cytokines in the pathogenesis of silicosis has become a hot topic，Th1/Th2relatedchemokines in the pathogenesis of silicosis are gaining importance. In order to explorethe roles of Th1and Th2related chemokines in the process of silicosis, we establishedexperimental silicosis rat model by SiO2instillation, monitored the expression of IP-10and TARC in the BALF and in the lungs of rats, T-bet is a Th1-specific transcriptionfactor，it play a decisive role in the Th1/Th2cell differentiation and play a keyregulatory role in the response of the T-cell differentiation. This study monitored theexpression of T-bet in lungs of model group and control group in order to discuss theroles of it in the pathogenesis of silicosis. Objective: To investigate the dynamic changes of chemokines in the BALF and in thelungs of model rats after one-time silica instillation. To investigate changes and theirsignificance of IP-10, TARC and T-bet in lungs of rat silicosis models at differentdevelopmental stages.Method: The experimental silicosis model in rats was established by intratrachealinstillation of silica. Each three rats from model group and control group were sacrificedrespectively on the1^st,7^th,14^th,21^st,28^th,35^th,77^th,106^th, and126thday after one-timeSilica dust instillation. Ligation of the right lung, the rat left lung lavage. Then collectthe BALF. The contents of IP-10and TARC in BALF were assayed by enzyme linkedimmunosorbent assay（ELISA）; the expressions of IP-10，TRAC and T-bet in rightlungs were observed by immunohistochemistry method.Result: The rat silicosis model was constructed successfully. In early stage of theexperimen(t1^st,7^th,14^th,21^stday), levels of IP-10in the lungs of silicotic rats obviouslyincreased than those in control group（P<0.05）, and in later stage of the experiment thelevels of IP-10had no obvious difference with control group（P>0.05）. The levels ofTARC in lungs of silicotic rats were higher than those in control group in early stage(1^st,7^th,14^th,21^st,28^th,35^thday)（P<0.05）and in later stage of experiment the levels had noobvious difference with control group（P>0.05）. Compared with the control group, theexpression of T-bet significantly enhanced（P<0.05）in the lung of the model rats on the1st,7th,14thand21stday; while reduced on the35^th,77^th,106^th, and126^thday（P<0.05）.Conclusion: Th1/Th2related chemokines play roles in the immune regulation processin rats with silicosis. At the early stage of the experiment（1-21d）, the increasedexpression of Th1related chemokine IP-10indicated that the cell-mediated immuneresponse by enhance Th1cells was predominant in the silicotic rats; while at the later stage（28-35d）, the expression of TARC which is a kind of Th2related chemokineenhanced significantly and the expression of IP-10reduced, suggesting that thecell-mediated immune response began to decrease and humoral immunity mediated byTh2cells began to increase. At the early stage of the experimen（t1-21d），the increasedexpression of T-bet indicated that it may be involved in the regulation of silicosis earlyfibrosis.