Interleukin-1 and Keratinocyte Growth Factor/Fibroblast Growth Factor-7 Gene Expression in Skin Experimental Irritant Contact Dermatitis Mouse Model Treated with Aqueous Extract of Trachyspermum copticum (L.) Link Seeds
Background: In our previous study, the extract of Trachyspermum copticum (L.) Link seeds on gene expression of IFN-γ and TGF-β1 in mouse model with irritant contact dermatitis (ICD), in comparison with cutaneous corticosteroids were evaluated. In that study, in addition to significantly increase of IFN-γ and TGF-β1 genes expression levels in skin samples of "mice with ICD" groups treated with extract in comparison to other groups, histopathologic findings showed substantial improvement of skin color, texture and thickness, and also significant increase in hair follicle number. Therefore, we have decided to study the levels of Interleukin-1 (IL-1) gene expression, which plays a major role in inflammation responses, and Keratinocyte Growth Factor/Fibroblast Growth Factor-7 (KGF/FGF-7), which has growth effect on cells and is an important endogenous mediator of hair follicle growth and development.
Materials and Methods: We used autopsy samples of skin lesions obtained from "mice model with irritant contact dermatitis (ICD)" from the previous study. In that study, "mice with ICD" divided in 9 groups and were treated with three concentrations of Trachyspermum Copticum (L.) Link dried seeds, cutaneous hydrocortisone, and fluocinolone acetonide. Then from the first day until the 10th day of treatment, clinical signs and histopathologic investigations were investigated. In the present study, using Real-Time PCR, the levels of IL-1 and KGF/FGF-7 genes expression in skin samples of inflammation site in above mice groups were studied. Statistical analysis, using one -way ANOVA, were performed. Level of significance was set at 0.05.
Results: The IL-1 gene expression showed a significant difference between groups: IL-1 gene expression levels in mice with ICD treated with extract and corticosteroids were higher than the other groups (p=0.0001). While in untreated "mice with ICD", no significant differences were observed. Also, during the treatment, there was a considerable increase in levels of IL-1 gene expression in groups treated with the extract at a rate of at least 2 to 3-fold in comparison with the "healthy untreated mice" group. The levels of KGF/FGF-7 gene expression in "mice with ICD" groups treated with the extract showed significance difference (p=0.014); also there was a meaningful difference in "mice with ICD" groups treated with cutaneous corticosteroids (p=0.004). While, in "untreated mice with ICD" group there were a significant decrease in the levels of KGF/FGF-7 gene expression in comparison with "healthy untreated mice" group (p=0.0001). Also, changes in the levels IL-1 and KGF/FGF-7 gene expressions in each group in different days were seen.
Conclusion: In this study, significant changes in the IL-1 and KGF/FGF-7 genes expression levels in the skin samples with inflammation, were associated with an increase in the rate and speed of improvement of contact dermatitis, more favorable conditions of the healed skin (in terms of color, consistency, and thickness), and a remarkable increase in the number of hair grown on the site of dermatitis (compared with control groups, and even groups with corticosteroid therapy).
Organization IL. ILO List of Occupational Diseases (revised 2010) Geneva, Switzerland, ILO (International Labour Organization); 2010[cited2010]. No.74: [Available from: http://www.ilo.org/safework/info/publications/WCMS_125137/lang--en/index.htm; Accessed. 2017.
Gibbs S. In vitro irritation models and immune reactions. Skin Pharmacology and Physiology. 2009;22(2):103-13.
Chew A, Maibach HI. Occupational issues of irritant contact dermatitis. International Archives of Occupational and Environmental Health. 2003;76(5):339–46.
Chew AL, Maibach HI. Ten genotypes of irritant contact dermatitis. In: Chew AL, Maibach HI, editors. Contact Dermatitis. Berlin, Germany: Springer. 2006; p:5–9.
Mirazi N, Vatanchian M. Effect of Olea europaea L. leaves aqueous extract on skin wound healing in male rat. Journal of Developmental Biology. 2011;3(9):7-14. (Full Text in Persian)
Zargari A. Medicinal plants. Tehran: Tehran University Press; 1990. (Full Text in Persian)
Hussein GH, Miyashiro H, Nakamura N, Hattori M, Kakiuchi N, Shimotohno K. Inhibitory effects of Sudanese medicinal plant extracts on hepatitis C virus (HCV) protease. Phytotherapy research. 2000;14:510–6.
Thangam C, Dhananjayan R. Antiinflammatory potential of the seeds of Carum copticum Linn. Indian Journal of Pharmacology. 2003;34:388-91.
Rasooli I, Fakoor MH, Yadegarinia D, Gachkar L, Allameh A, Rezaei MB. Antimycotoxigenic characteristics of Rosmarinus officinalis and Trachyspermum copticum L. essential oils. International Journal of Food Microbiology. 2008;122:135-9.
Anis M, Iqbal M. Antipyretic utility of some Indian plants in traditional medicine. Fitoterapia. 1986;57:52-5.
Mathew N, Misra-Bhattacharya S, Perumal V, Muthuswamy K. Antifilarial Lead molecules isolated from Trachyspermum ammi. Molecules. 2008;13(9):2156-68.
Dashti-Rahmatabadi MH, Hejazian SH, Morshedi A, Rafati A. The analgesic effect of Carum copticum extract and morphine on phasic pain in mice. Journal of Ethnopharmacology. 2007;109:226-8.
Kaur T, Bijarnia RK, Singla SK, Tandon C. In vivo efficacy of Trachyspermum ammi anticalcifying protein in urolithiatic rat model. Journal of Ethnopharmacology. 2009;126:459-62.
Hejazian SH, Mosaddegh MH, Dashti Rahmatabadi H. Antinociceptive effects ofCarum copticum extracts in mice using formalin test. World Applied Sciences Journal. 2008;34:388–391.
Bera D, Lahiri D, Nag A. Novel natural antioxidant for stabilization of edible oil: the ajowan (Carum copticum) extract case. Journal of the American Oil Chemists' Society. 2004;81:169–172.
Malekpour M, Karimi F, Anissian A, Kamalinejad M, Bandehpour M, Soori H., et al. Evaluation of Effect of Non-cytotoxic Aqueous Extract Concentrations of Dried Seeds of Trachyspermum copticum (L.) Link (Zenian) on Irritant Contact Hypersensitivity Induced by 2,4- Dinitorchlorobenzene (DNCB) in BALB/c Mouse Model [Research Thesis]. Tehran, Iran.: Shahid Beheshti University of Medical Sciences. 2014. (Full Text in Persian)
Slodownik D, Lee A, Nixon R. Irritant contact dermatitis: a review. Australasian Journal of Dermatology. 2008;49(1):1-9.
Takayuki Yoshimoto TY, editor. Cytokine Frontiers: Springer Tokyo Heidelberg New York Dordrecht London; 2014.
Yen TT, Thao DT, Thuoc TL. An overview on keratinocyte growth factor: from the molecular properties to clinical applications. Protein and Peptide Letters. 2014;21(3):306-17.
Booth C, Potten CS. Keratinocyte growth factor increases hair follicle survival following cytotoxic insult. Journal of Investigative Dermatology. 2000;114(4):667-73.
Kawano M, Komi-Kuramochi A, Asada M, Suzuki M, Oki J, Jiang J, et al. Comprehensive analysis of FGF and FGFR expression in skin: FGF18 is highly expressed in hair follicles and capable of inducing anagen from telogen stage hair follicles. Journal of investigative dermatology. Journal of Investigative Immunology. 2005;124(5):877-85.
Beer HD, Gassmann MG, Munz B, Steiling H, Engelhardt F, Bleuel K, et al. Expression and function of keratinocyte growth factor and activin in skin morphogenesis and cutaneous wound repair. Journal of Investigative Dermatology, Symposium proceedings. 2000;5(1):34-9.
Erdag G, Medalie DA, Rakhorst H, Krueger GG, Morgan JR. FGF-7 expression enhances the performance of bioengineered skin. Molecular Therapy. 2004;10(1):76-85.