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Lichen planus: altered AIM2 and NLRP1 expression in skin lesions and defective activation in peripheral blood mononuclear cells.
Clin Exp Dermatol 2019; 44(4):e89-e95CE

Abstract

BACKGROUND

Lichen planus (LP) is an inflammatory skin disease with unknown aetiology. Activation by pathogen-associated molecular patterns or environmental stimuli may activate some components of inflammasomes that contribute to the inflammatory process in LP lesions.

AIM

To characterize the inflammasomes in skin lesions and peripheral blood mononuclear cells (PBMCs) of patients with LP under Toll-like receptor (TLR) activation.

METHODS

In total, 15 patients with LP and 14 healthy controls (HCs) were enrolled in the study. Inflammasome expression in skin was evaluated by real-time PCR and immunohistochemistry, while ELISA was used to assess the production of interleukin (IL)-1β by PBMCs under stimulation with TLR4 and TLR7/TLR8 agonists and adenosine triphosphate (ATP).

RESULTS

Compared with the levels in HC samples, increased expression of the inflammasome AIM2 was verified in both epidermal and dermal sections of LP skin lesions, whereas NLRP1 and IL-β expression levels were enhanced in the dermis. LP skin lesion samples exhibited higher AIM2 transcript levels, similar NLRP1 levels and lower pro-IL-1β mRNA levels compared with HC samples. We verified that, compared with PBMCs from HC subjects, PBMCs from patients with LP produced similar amounts of IL-1β after induction by TLR4 agonists but lower IL-1β levels after induction by TLR7/TLR8 agonists, regardless of the addition of ATP.

CONCLUSION

Alterations in innate immunity, such as inflammasome component expression in skin lesions and PBMCs, were observed in patients with LP. Further investigations of dysfunctional inflammasome activation and the chronic inflammatory status of LP are required.

Authors+Show Affiliations

Laboratory of Investigation in Medicine, LIM-56, Department of Dermatology, Tropical Medicine Institute of São Paulo, University of São Paulo Medical School, São Paulo, Brazil.Laboratory of Investigation in Medicine, LIM-56, Department of Dermatology, Tropical Medicine Institute of São Paulo, University of São Paulo Medical School, São Paulo, Brazil.Laboratory of Investigation in Medicine, LIM-56, Department of Dermatology, Tropical Medicine Institute of São Paulo, University of São Paulo Medical School, São Paulo, Brazil.Laboratory of Investigation in Medicine, LIM-56, Department of Dermatology, Tropical Medicine Institute of São Paulo, University of São Paulo Medical School, São Paulo, Brazil.Laboratory of Investigation in Medicine, LIM-56, Department of Dermatology, Tropical Medicine Institute of São Paulo, University of São Paulo Medical School, São Paulo, Brazil.Department of Pathology, University of São Paulo Medical School, São Paulo, Brazil.Laboratory of Investigation in Medicine, LIM-56, Department of Dermatology, Tropical Medicine Institute of São Paulo, University of São Paulo Medical School, São Paulo, Brazil.Laboratory of Investigation in Medicine, LIM-56, Department of Dermatology, Tropical Medicine Institute of São Paulo, University of São Paulo Medical School, São Paulo, Brazil. Department of Pathology, University of São Paulo Medical School, São Paulo, Brazil.Laboratory of Investigation in Medicine, LIM-56, Department of Dermatology, Tropical Medicine Institute of São Paulo, University of São Paulo Medical School, São Paulo, Brazil.

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

30552699

Citation

Domingues, R, et al. "Lichen Planus: Altered AIM2 and NLRP1 Expression in Skin Lesions and Defective Activation in Peripheral Blood Mononuclear Cells." Clinical and Experimental Dermatology, vol. 44, no. 4, 2019, pp. e89-e95.
Domingues R, Pietrobon AJ, Carvalho GC, et al. Lichen planus: altered AIM2 and NLRP1 expression in skin lesions and defective activation in peripheral blood mononuclear cells. Clin Exp Dermatol. 2019;44(4):e89-e95.
Domingues, R., Pietrobon, A. J., Carvalho, G. C., Pereira, N. Z., Pereira, N. V., Sotto, M. N., ... Sato, M. N. (2019). Lichen planus: altered AIM2 and NLRP1 expression in skin lesions and defective activation in peripheral blood mononuclear cells. Clinical and Experimental Dermatology, 44(4), pp. e89-e95. doi:10.1111/ced.13859.
Domingues R, et al. Lichen Planus: Altered AIM2 and NLRP1 Expression in Skin Lesions and Defective Activation in Peripheral Blood Mononuclear Cells. Clin Exp Dermatol. 2019;44(4):e89-e95. PubMed PMID: 30552699.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Lichen planus: altered AIM2 and NLRP1 expression in skin lesions and defective activation in peripheral blood mononuclear cells. AU - Domingues,R, AU - Pietrobon,A J, AU - Carvalho,G C, AU - Pereira,N Z, AU - Pereira,N V, AU - Sotto,M N, AU - Aoki,V, AU - Duarte,A J S, AU - Sato,M N, Y1 - 2018/12/14/ PY - 2018/09/26/accepted PY - 2018/12/16/pubmed PY - 2020/1/7/medline PY - 2018/12/16/entrez SP - e89 EP - e95 JF - Clinical and experimental dermatology JO - Clin. Exp. Dermatol. VL - 44 IS - 4 N2 - BACKGROUND: Lichen planus (LP) is an inflammatory skin disease with unknown aetiology. Activation by pathogen-associated molecular patterns or environmental stimuli may activate some components of inflammasomes that contribute to the inflammatory process in LP lesions. AIM: To characterize the inflammasomes in skin lesions and peripheral blood mononuclear cells (PBMCs) of patients with LP under Toll-like receptor (TLR) activation. METHODS: In total, 15 patients with LP and 14 healthy controls (HCs) were enrolled in the study. Inflammasome expression in skin was evaluated by real-time PCR and immunohistochemistry, while ELISA was used to assess the production of interleukin (IL)-1β by PBMCs under stimulation with TLR4 and TLR7/TLR8 agonists and adenosine triphosphate (ATP). RESULTS: Compared with the levels in HC samples, increased expression of the inflammasome AIM2 was verified in both epidermal and dermal sections of LP skin lesions, whereas NLRP1 and IL-β expression levels were enhanced in the dermis. LP skin lesion samples exhibited higher AIM2 transcript levels, similar NLRP1 levels and lower pro-IL-1β mRNA levels compared with HC samples. We verified that, compared with PBMCs from HC subjects, PBMCs from patients with LP produced similar amounts of IL-1β after induction by TLR4 agonists but lower IL-1β levels after induction by TLR7/TLR8 agonists, regardless of the addition of ATP. CONCLUSION: Alterations in innate immunity, such as inflammasome component expression in skin lesions and PBMCs, were observed in patients with LP. Further investigations of dysfunctional inflammasome activation and the chronic inflammatory status of LP are required. SN - 1365-2230 UR - https://www.unboundmedicine.com/medline/citation/30552699/Lichen_planus:_altered_AIM2_and_NLRP1_expression_in_skin_lesions_and_defective_activation_in_peripheral_blood_mononuclear_cells_ L2 - https://doi.org/10.1111/ced.13859 DB - PRIME DP - Unbound Medicine ER -