In situ detection of SOCS and cytokine expression in the uterine cervix from HIV/HPV coinfected women.
The purpose of this study was to look for associations between a newly described class of suppressors of cytokine signaling (SSI/SOCS) and cytokine expression in the uterine cervix from HIV/HPV coinfected women. We examined the pro-inflammatory cytokines TNF-alpha and IL-6 since their expressions are linked and responsible for many aspects of both localized and systemic inflammatory responses. Further, expression of SSI/SOCS has been implicated in the negative feedback regulation of cytokine receptor signaling. PCR-amplified HIV-1 cDNA was noted mainly in the stroma, showing a perivascular distribution, and most of the infected cells colabeled with the macrophage marker CD68. The distribution of IL-6 and TNF-alpha was in the same area to HIV-1 and much greater than normal cervices from women with no evidence of viral infection. SOCS/SSI-1 and -3 mRNA positive cells in the uterine cervix were commonly detected in these noninfected cervical tissues; however, very few cells that contained SOCS were evident in areas where HIV-1, TNF-alpha, and IL-6 expressing cells were found. This suggests that viral-related suppression of SOCS/SSI-1-3 expression may be a factor in the marked local enhancement of TNF-alpha and IL-6 production which, in turn, may help facilitate viral spread; however, further studies should be done in order to elucidate the exact mechanisms of SOCS in the cervix.
Nicol
A F
AF
Immunology Service of Evandro Chagas Clinical Research Institute, IPEC, FIOCRUZ, Avenue Brazil 4365 Manguinhos, Rio de Janeiro, CEP 21045-900, Brazil. nicol@ioc.fiocruz.br
Nuovo
G J
GJ
Wang
Y
Y
Grinsztejn
B
B
Tristão
A
A
Russomano
F
F
Perez
M A
MA
Lapa e Silva
J R
JR
Fernandes
A T G
AT
Gage
J R
JR
Martínez-Maza
O
O
Bonecini-Almeida
M G
MG
D000328:Adult; D051940:B7-2 Antigen / Q000235:genetics / Q000378:metabolism; D002584:Cervix Uteri / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000276:immunology / Q000378:metabolism*; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D027383:Papillomaviridae / Q000302:isolation & purification; D030361:Papillomavirus Infections / Q000150:complications / Q000276:immunology / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
D051940:B7-2 Antigen; D016207:Cytokines; D004279:DNA, Viral; D015850:Interleukin-6; D012333:RNA, Messenger; D050826:Suppressor of Cytokine Signaling Proteins; D014409:Tumor Necrosis Factor-alpha