Differential stimulation of IgE production, STAT activation and cytokine and CD86 expression by 2,4-dinitrochlorobenzene and trimellitic anhydride.
It has been reported that dermal exposure to trimellitic anhydride (TMA, 50%), a respiratory allergen, induced greater production of serum IgE and expression of Th2 cytokines than 2,4-dinitrochlorobenzene (DNCB, 1%), a potent contact sensitizer, in female BALB/C mice. To determine if there is any strain difference, four strains (B6C3F1, C57BL/6, BDF1 and BALB/C) of female mice were employed in this study to compare the differential effects of these chemicals on the hypersensitivity responses. Serum IgE levels were increased in TMA-treated B6C3F1, C57BL/6 and BDF1 mice when compared with the DNCB treatment and vehicle controls; in contrast, no difference was observed between TMA- and DNCB-treated BALB/C mice, although both chemicals induced greater IgE production than vehicle controls. In vitro expression of interleukin 4 (IL-4) and IL-13 mRNA by overnight concanavalin A (ConA)-stimulated draining lymph node cells was enhanced following in vivo treatment with TMA but not with DNCB in the B6C3F1, C57BL/6 and BDF1 mice. In contrast, TMA and DNCB induced similar levels of IL-4 and IL-13 mRNA in the BALB/C mice. The IL-4 protein levels in the supernatants of overnight ConA-treated draining lymph node cells were also increased in TMA-treated B6C3F1 and C57BL/6 mice when compared with the DNCB treatment and vehicle controls. Further mechanistic evaluation in the B6C3F1 mice indicated that the activation of STAT6 but not STAT4 by ConA plus IL-2-treated draining lymph node cells was increased in TMA- but not DNCB-treated mice when compared with the vehicle controls. Furthermore, surface expression of B7.2 (CD86) by B cells was increased in both TMA- and DNCB-treated B6C3F1 mice when compared with the vehicles; however, greater B7.2 expression was observed in TMA-treated compared with DNCB-treated. Overall, these results demonstrate that a similar pattern of IgE and cytokine production was observed in these strains of mice except for BALB/C. Furthermore, differential activation of STAT6 and expression of CD86 following exposure to TMA and DNCB may contribute to the differential production of IgE and cytokines.
Guo
T L
TL
Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA 23298-0613, USA.
Zhang
X L
XL
Leffel
E K
EK
Peachee
V L
VL
Karrow
N A
NA
Germolec
D R
DR
White
K L
KL
D000279:Administration, Cutaneous; D000485:Allergens / Q000008:administration & dosage / Q000633:toxicity; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis*; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051940:B7-2 Antigen; D016207:Cytokines / Q000096:biosynthesis* / Q000097:blood; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004137:Dinitrochlorobenzene / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D006241:Haptens / Q000008:administration & dosage / Q000633:toxicity; D007073:Immunoglobulin E / Q000096:biosynthesis* / Q000097:blood; D007371:Interferon-gamma / Q000096:biosynthesis / Q000097:blood; D018793:Interleukin-13 / Q000096:biosynthesis / Q000097:blood; D015847:Interleukin-4 / Q000096:biosynthesis / Q000097:blood; D008198:Lymph Nodes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D051379:Mice; D008815:Mice, Inbred Strains; D010796:Phthalic Anhydrides / Q000008:administration & dosage / Q000633:toxicity*; D050797:STAT4 Transcription Factor; D050800:STAT6 Transcription Factor; D013045:Species Specificity; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism*
D000485:Allergens; D015703:Antigens, CD; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D016207:Cytokines; D004268:DNA-Binding Proteins; D004137:Dinitrochlorobenzene; D006241:Haptens; D018793:Interleukin-13; D008562:Membrane Glycoproteins; D010796:Phthalic Anhydrides; D050797:STAT4 Transcription Factor; D050800:STAT6 Transcription Factor; C494091:Stat4 protein, mouse; C494100:Stat6 protein, mouse; D015534:Trans-Activators; D015847:Interleukin-4; D007073:Immunoglobulin E; C015559:trimellitic anhydride; D007371:Interferon-gamma