Local cytokine and inflammatory responses to candidate vaginal adjuvants in mice.
The current study was undertaken to explore the correlation of adjuvanticity and local inflammatory response elicited in the murine vagina and the draining lymph nodes following local administration of two candidate vaginal adjuvants, Toll like receptor (TLR) 9 agonist CpG ODN, and a non-TLR targeting molecule alpha-galactosylceramide (alpha-GalCer). Using real-time PCR array analysis, we could show that a group of 13 common cytokine genes are activated in the vagina within 24h after vaginal administration of these adjuvants, including Ccl2, Ccl7, Ccl12, Ccl19, Ccl20, Ccl22, Cxcl1, Cxcl5, Il10 and the Th1-inducing molecules Ifng, Cxcl9, Cxcl10 and Cxcl11. A high degree of inflammation in and damage to the epithelium was exclusively observed in the vagina of the CpG ODN treated mice, which was reversed within 48h. These results indicate that there is a group of common genes that correlate with the adjuvanticity of CpG ODN and alpha-GalCer in the vagina, and that alpha-GalCer induces less of local inflammatory reactions in the murine vagina compared to CpG ODN.
Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Medicinaregatan 7A, 40530 Gothenburg, Sweden.
Madelene
M
Lindqvist
Nazanin
N
Navabi
Marianne
M
Jansson
Emma
E
Samuelson
Asa
A
Sjöling
Charlotte
C
Orndal
Ali M
AM
Harandi
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000282:Administration, Intravaginal; D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000276:immunology*; D004848:Epithelium / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D005260:Female; D005699:Galactosylceramides / Q000494:pharmacology*; D020869:Gene Expression Profiling; D018928:Immunity, Mucosal; D008198:Lymph Nodes / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018675:Toxicity Tests; D014621:Vagina / Q000187:drug effects / Q000276:immunology* / Q000473:pathology
D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D016207:Cytokines; D005699:Galactosylceramides; D009838:Oligodeoxyribonucleotides; C493154:alpha-galactosylceramide