Airway epithelial cells increase macrophage chemotaxis and inflammatory cytokine secretion under hypoxic conditions.
	    		
		   		
		   			
		   		
	    	
    	 
    	10.11817/j.issn.1672-7347.2019.02.004
   		
        
        	
        	
        	
        		- Author:
	        		
		        		
		        		
			        		Xingwu CHEN
			        		
			        		
			        		
			        			1
			        			,
			        		
			        			2
			        			
			        		
			        		
			        		
			        		
			        		;
		        		
		        		
		        		
			        		Lilong QING
			        		
			        		
			        		
			        			3
			        			
			        		
			        		
			        		
			        		
			        		;
		        		
		        		
		        		
			        		Zhengui SUN
			        		
			        		
			        		
			        			3
			        			
			        		
			        		
			        		
			        		
			        		;
		        		
		        		
		        		
			        		Min XING
			        		
			        		
			        		
			        			3
			        			
			        		
			        		
			        		
			        		
			        		;
		        		
		        		
		        		
			        		Leilei ZANG
			        		
			        		
			        		
			        			3
			        			
			        		
			        		
			        		
			        		
			        		;
		        		
		        		
		        		
			        		Hanli WANG
			        		
			        		
			        		
			        			3
			        			
			        		
			        		
			        		
			        		
			        		
		        		
		        		
		        		
		        		
		        			
			        		
			        		Author Information
			        		
		        		
		        		
			        		
			        		
			        			1. Department of Respiratory, First Affiliated Hospital, Wannan Medical College, Wuhu Anhui 241001, China cxw0028@
			        		
			        			2. com.
			        		
			        			3. Department of Respiratory, First Affiliated Hospital, Wannan Medical College, Wuhu Anhui 241001, China.
			        		
		        		
	        		
        		 
        	
        	
        	
        		- Publication Type:Journal Article
 
        	
        	
            
            	- MeSH:
            	
	        			
	        				
	        				
				        		
					        		Cell Hypoxia;
				        		
			        		
				        		
					        		Chemotaxis;
				        		
			        		
				        		
					        		Cytokines;
				        		
			        		
				        		
					        		Epithelial Cells;
				        		
			        		
				        		
					        		Humans;
				        		
			        		
				        		
					        		Hypoxia-Inducible Factor 1, alpha Subunit;
				        		
			        		
				        		
					        		Macrophages
				        		
			        		
	        			
	        			
            	
            	
 
            
            
            	- From:
	            		
	            			Journal of Central South University(Medical Sciences)
	            		
	            		 2019;44(2):134-143
	            	
            	
 
            
            
            	- CountryChina
 
            
            
            	- Language:Chinese
 
            
            
            	- 
		        	Abstract:
			       	
			       		
				        
				        	To investigate the effects of airway epithelial cells on macrophages chemotaxis and inflammatory cytokine expression under hypoxic conditions.
 Methods: Human bronchial epithelial cells (HBE) treated with different concentrations (0, 100, 200, 400, 800 μmol/L) of CoCl2 or transfected with HIF-1α siRNA were co-cultured with THP-1-derived M1 macrophages or M2 macrophages. The chemotactic effects on macrophages were analyzed by Transwell assay. The levels of TNF-α, IFN-γ, IL-4, IL-13 and IL-10 in the supernatants of macrophages were detected by ELISA, and HIF-1α or Cav-1 mRNA expression in HBE or macrophages was detected by RT-qPCR.
 Results: HBE cells promoted macrophages chemotaxis in a time- and concentration-dependent manner. Compared to un-transfected group, the chemotactic ability of HBE transfected with HIF-1α siRNA was significantly weakened (P<0.01). Under the same culture conditions, the chemotaxis of M2 macrophages was greater than that in THP1-derived M1 macrophages. The concentrations of TNF-α, IFN-γ, IL-4, IL-13 and IL-10 in the supernatants of macrophages were increased in a time-and concentration-dependent manner. The concentrations of TNF-α and IFN-γ were increased further after co-culturing for 8 and 12 h; while IL-4, IL-13 and IL-10 concentrations were increased further during 24 h of co-culture. The levels of cytokines in the supernatants of macrophages co-cultured with HBE and transfected with HIF-1α siRNA were significantly lower than those in un-transfected cells (P<0.05 or P<0.01). The reduction of TNF-α or IFN-γ was more obvious. The expression of HIF-1α or Cav-1 mRNA in HBE or macrophages was increased in a concentration-dependent manner after 8 or 12 h co-culture, which was significantly reduced when HBE was transfected with HIF-1α siRNA.
 Conclusion: Airway epithelial cells can enhance macrophages chemotaxis and pro-inflammatory cytokines expressions under hypoxic condition. HIF-1α and Cav-1 may be the important mediators in these processes.