Atopic dermatitis-associated protein interaction network lead to new insights in chronic sulfur mustard skin lesion mechanisms

Abstract

Chronic sulfur mustard skin lesions (CSMSLs) are the most common complications of sulfur mustard exposure; however, its mechanism is not completely understood.According to clinical signs, there are similarities between CSMSL and atopic dermatitis (AD). In this study, proteomic results of AD were reviewed and the AD-associated protein–protein interaction network (PIN) was analyzed. According to centrality measurements, 16 proteins were designated as pivotal elements in AD mechanisms. Interestingly, most of these proteins had been reported in some sulfur mustard-related studies in late and acute phases separately. Based on the gene enrichment analysis, aging, cell response to stress, cancer, Toll- and NOD-like receptor and apoptosis signaling pathways have the greatest impact on the disease. By the analysis of directed protein interaction networks, it is concluded that TNF, IL-6, AKT1, NOS3 and CDKN1A are the most important proteins. It is possible that these proteins play role in the shared complications of AD and CSMSL including xerosis and itching.

Keywords::

• acute sulfur mustard skin lesion
• atopic dermatitis
• chronic sulfur mustard skin lesion
• protein interaction network
• proteomics

Acknowledgements

The authors thank the public archive of Chemical Injuries Research Center, Tehran, Iran, for the images used in Figure 1 and also Dr. Seyed-Naser Emadi who provided the real images of late complications of mustard gas in cutaneous exposure and Dr. Mehdi Mirzaie for his comments during this study.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Writing assistance from Radan English Edit was utilized in the production of this manuscript.

Key issues

• • Chronic sulfur mustard skin lesions (CSMSLs) are the most common complications in victims of the chemical warfare.

• • There are several clinical similarities between CSMSL and atopic dermatitis (AD).

• • Recent proteomic studies of AD were reviewed and AD-associated protein–protein interaction network (PIN) were also analyzed.

• • Sixteen proteins were designated as pivotal elements in AD mechanism based on centrality parameters.

• • Twelve of these 16 proteins had been reported in some SM-related studies in late and acute phases separately.

• • Aging, cell response to stress, cancer, Toll-like receptor, NOD-like receptor and apoptosis signaling pathways are the dominant active mechanism in AD and CSMSL.

• • By the analysis of directed PIN, it is concluded that TNF, IL-6, AKT1, NOS3 and CDKN1A possibly role in the shared complications of the AD and CSMSL.