Proinflammatory and regulatory mechanisms in allergic contact dermatitis caused by methylchloroisothiazolinone and methylisothiazolinone

• DOI: 10.1111/exd.14086
• Publication Date: 2020-02-12T16:44:00Z
• Authors: Heliana Freitas d...; Anangelica Rodrig...; Gabriel Costa de ...; Anna Julia Pietrobon; Anna Cláudia Calv...; Luanda Mara da Si...; Iara G. Fernandes; Naiura Vieira Per...; Mírian Nacagami S...; Vitor Manoel Silv...; Maria Notomi Sato
• Keywords: Adult; Inflammation; Male; Interleukin-6; Tumor Necrosis Factor-alpha; Interleukin-1beta; Forkhead Transcription Factors; Middle Aged; Interleukin-10; 3. Good health; Toll-Like Receptor 4; Transforming Growth Factor beta1; Mice; Thiazoles; 03 medical and health sciences; 0302 clinical medicine; Dermatitis, Allergic Contact; Leukocytes, Mononuclear; Animals; Cytokines; Humans; Female; Signal Transduction

AbstractBackgroundMethylchloroisothiazolinone (MCI) and methylisothiazolinone (MI) are the cause of an increasing number of contact allergies. Understanding the mechanisms by which MCI/MI induces proinflammatory and regulatory factors production is necessary to understand the outcome of allergic contact dermatitis (ACD).ObjectivesTo evaluate the dysfunction of proinflammatory cytokines and regulatory factors in the positive MCI/MI patch test at the transcriptional and protein expression levels. Moreover, to analyse the cytokines production induced by MI in peripheral blood mononuclear cells (PBMCs).Materials and MethodsThe selected patients had positive MCI/MI patch test results. The expression of proinflammatory factors was evaluated by q‐PCR and immunochemistry at 48 hours of positive MCI/MI patch test. The MCI/MI‐ or MI‐ induced secretion of IL‐1β, TNF and IL‐6 by PBMC was analysed by flow cytometry.ResultsThe results showed a decreased TLR4 expression with upregulated IL6, FOXP3, IL10 and TGFβ mRNA expression as assessed by q‐PCR at the site of the MCI/MI skin reaction. We detected increased protein levels of TLR4, FOXP3 and IL‐10 in the dermis layer in the ACD reaction by immunocitochemistry. Moreover, MCI/MI induced proinflammatory cytokine production by PBMC through the NF‐κB signalling pathway.ConclusionConsidering the altered innate immune response triggered by MCI/MI sensitization, these findings indicate that the regulatory process at the induction phase of ACD is a crucial mechanism. Given the increase in occupational and domestic exposure to MCI/MI, the underlying immunological mechanisms should be understood.