Expression and secretion of CXCL-8 and CXCL-10 from mycobacterium bovis BCG-infected human epithelial cells: role of IL-4.
CXC chemokine release can be modulated by Th2-derived cytokines. Interleukin(IL)-4 is one of the cytokines that are the hallmark of the Th-2 response, and plays an important role in human tuberculosis. In the current study, we investigated the effect of IL-4 on chemokine production by human epithelial cells infected with Mycobacterium bovis bacillus calmette-guérin (BCG). Gene expression of CXCL-8 and CXCL-10 was determined by the reverse transcription (RT)-polymerase chain reaction method. The levels of immunoreactive CXCL-8 and CXCL-10 were determined by enzyme-linked immunosorbent assay. We found that, although M. bovis BCG induced gene expression of CXCL-8 and CXCL-10 in M. bovis BCG-infected human epithelial cells, CXCL-8 mRNA level was significantly reduced by IL-4, whereas no significant effect of IL-4 was observed on CXCL10 mRNA level. In addition, IL-4 decreased CXCL-8 (in a graded and significant manner) but not CXCL-10 secretion. These results were further confirmed, since a significant reversion was obtained with a neutralizing antibody to human IL-4, whereas an isotype-matched control antibody had no significant effect on CXCL-8 secretion. Furthermore, we found a similar effect of IL-4 on M. bovis BCG-induced CXCL-8 and CXCL-10 secretion by using other human epithelial A549 cell line. Collectively, these data demonstrate that M. bovis BCG-infected human epithelial cells can have an active role in a local inflammatory immune response via the secretion of CXC chemokines which can be selectively regulated by Th2-derived cytokines.
Méndez-Samperio
Patricia
P
Departamento de Immunología, Escuela Nacional de Ciencias Biológias, IPN, Carpio y Plan de Ayala, México, DF 11340, México.
Miranda
Elena
E
Vázquez
Abraham
A
D045744:Cell Line, Tumor; D054357:Chemokine CXCL10; D018925:Chemokines / Q000378:metabolism; D019743:Chemokines, CXC / Q000096:biosynthesis* / Q000378:metabolism; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000378:metabolism / Q000382:microbiology*; D005786:Gene Expression Regulation; D006801:Humans; D015847:Interleukin-4 / Q000378:metabolism / Q000502:physiology*; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000378:metabolism; D009163:Mycobacterium bovis / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry; D018418:Th2 Cells / Q000378:metabolism
C114753:CXCL10 protein, human; C508606:CXCL8 protein, human; D054357:Chemokine CXCL10; D018925:Chemokines; D019743:Chemokines, CXC; D016209:Interleukin-8; D012333:RNA, Messenger; D011994:Recombinant Proteins; D015847:Interleukin-4