Tacrolimus Modulates Dendritic Cell Activation in the Sensitization Phase of Allergic Contact Dermatitis

Abstract

Background: Knowledge of the effect of topically applied calcineurin antagonists such as tacrolimus on the sensitization phase of allergic contact dermatitis is currently limited. Objective: To investigate tacrolimus-dependent immunomodulation on gene expression alterations in human antigen-presenting cells which are stimulated with small-molecular-weight contact allergens. Methods: Monocyte-derived dendritic cells (moDC) and THP-1 cells were stimulated with the contact sensitizer cinnamic aldehyde (CAld) and compared with the very strong experimental sensitizer 2,4,6-trinitrobenzene sulfonic acid (TNBS) in vitro. Quantitative PCR analysis was used to detect gene expression changes, particularly of interleukin (IL) 8, as an indicator of differential dendritic cell (DC) gene expression after sensitizer stimulation in the absence or presence of tacrolimus and betamethasone at two different concentrations. Results: DC activation was clearly demonstrated by a significant IL-8 upregulation after 24 h, whereas tacrolimus or betamethasone alone did not affect IL-8 baseline expression. Betamethasone and, to a lesser extent, tacrolimus led to a marked reduction of chemical-induced IL-8 expression by TNBS and CAld. Conclusion: The results of the present study support the hypothesis that the calcineurin inhibitor tacrolimus has modulatory effects on human antigen-presenting cells during the sensitization phase of allergic contact dermatitis. In addition, moDC as well as THP-1 cells may serve as a system to study immune-modulating effects of drugs such as glucocorticoids or calcineurin antagonists.

Allergic Contact Dermatitis (ACD) by Anti-allergic Agents

“…Usually, severe cases are treated with systemic corticosteroids which may be tapered gradually. Tacrolimus ointment and eye drop can also be used additionally to the corticosteroid or instead of these [4,5]. Oral steroid may also be used in more severe cases to relieve the intense itching.…”

Hapten may play an important role in food allergen-related intestinal immune inflammation

“…As a strong experimental sensitizer, TNBS was used in vitro in induction of allergic contact dermatitis[22], TNBS is a classical skin contactant which can induce delayed hypersensitivity reactions when applied to the skin because it haptenates body proteins with trinitrophenyl (TNP) groups and renders such self-protein immunogenic to the immune system. While, when TNBS is introduced into the colon of susceptible mice via intra-rectal instillation, it induces T cell-mediated immune response in the colonic mucosa, in this case leading to a massive mucosal inflammation characterized by the dense infiltration of T cells and macrophages throughout the entire wall of the large bowel, TNBS-colitis is regarded as Thl T cell-mediated inflammation[232425].…”

CD4+ T cell responses in Balb/c mice with food allergy induced by trinitrobenzene sulfonic acid and ovalbumin

“…In addition, certain drugs, such as haptens, induce adverse reactions including drug hypersensitivity, with this occurring in approximately 7% of the population when drugs are absorbed and combined with self-protein (11,12). Trinitrobenzene sulfonic acid (TNBS), as a chemical hapten, and is frequently used in the induction of atopic disease in the laboratory (13), and has been demonstrated to result in a T cell-mediated immune response in the colonic mucosa in susceptible mice when administered rectally (14,15). With the increase of atopic diseases, dietary hapten exposure has additionally increased via different means, including processed food, oral antibiotics, formula milk and drug use (8,16).…”