Temporal changes in cytokine gene expression profiles induced in mice by trimellitic anhydride.
Prolonged (13 day) topical exposure of BALB/c strain mice to the chemical respiratory allergen trimellitic anhydride (TMA) induces a selective T helper (Th) 2 profile of cytokine secretion in cells isolated from the draining lymph node. The ability of chemical respiratory allergens to elicit preferential type 2 immune responses is a distinguishing characteristic and provides the theoretical basis for cytokine fingerprinting, a novel approach to hazard identification. This study aimed to further characterize the cytokine expression profile induced by TMA, and to investigate the kinetics of cytokine production at both the protein and mRNA level by comparison of acute (3 day) and chronic (13 day) exposure regimes. Acute exposure resulted in the expression of high levels of mRNA for both Th1- and Th2-type cytokines, including interleukins 4, 10, 15 (IL-4, IL-10, IL-15) and interferon gamma (IFN-gamma), and the inflammatory cytokine IL-6, as determined by ribonuclease protection assay (RPA). However, following chronic exposure marked down-regulation of message for IL-6 and IFN-gamma was observed along with concomitant up-regulation of IL-4 and IL-10 expression. These cytokine mRNA profiles were broadly paralleled at the protein level. There was also a marked increase with time of mRNA for the Th2 cytokine IL-9, a cytokine not associated previously with chemical allergy. These data show that as the immune response to TMA develops, the cytokine gene expression profile of allergen-activated lymph node cells evolves from a mixed Th1/Th2 phenotype to a more polarized Th2 profile.
Betts
Catherine J
CJ
Syngenta Central Toxicology Laboratory, Alderley Park, Macclesfield, Cheshire, UK. catherine.betts@syngenta.com
Dearman
Rebecca J
RJ
Flanagan
Brian F
BF
Kimber
Ian
I
D000818:Animals; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism; D004334:Drug Administration Schedule; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D008198:Lymph Nodes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D023282:Nuclease Protection Assays; D010796:Phthalic Anhydrides / Q000008:administration & dosage / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D016207:Cytokines; D010796:Phthalic Anhydrides; D012333:RNA, Messenger; C015559:trimellitic anhydride