Interleukin-6 serum level and gene polymorphism in keloid patients

Azza Mohamed Kamel Abdu Allah; Kawthar Ibraheem Mohammed; Azza Gaber Antar Farag; Magda Mostafa Hagag; Mai Essam; Nermin Reda Tayel

doi:10.14715/cmb/2019.65.5.7

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Vol. 65 No. 5: Issue 5

Issue Published : July 13, 2019

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Interleukin-6 serum level and gene polymorphism in keloid patients

https://doi.org/10.14715/cmb/2019.65.5.7

Azza Mohamed Kamel Abdu Allah

Department of Biochemistry and Molecular Biology, Faculty of Medicine, Menoufia University, Egypt

Kawthar Ibraheem Mohammed

Department of Medical Microbiology and Immunology, Faculty of Medicine, Ain Shams University Egypt and Associate professor at Taibah University KSA

Azza Gaber Antar Farag

Department of Dermatology, Andrology and STDs, Faculty of medicine, Menoufia University, Egypt

Magda Mostafa Hagag

Department of Dermatology, Andrology and STDs, Faculty of medicine, Menoufia University, Egypt

Mai Essam

Department of Dermatology, Andrology and STDs, Faculty of medicine, Menoufia University, Egypt

Nermin Reda Tayel

Department of Molecular Diagnostics and Therapeutic Genetic Engineering and Biotechnology Research Institute, Egypt

Corresponding Author(s) : Azza Mohamed Kamel Abdu Allah

azza.abdallah@yahoo.com

Cellular and Molecular Biology, Vol. 65 No. 5: Issue 5
Article Published : June 30, 2019

Abstract

The formation of keloid is associated with accumulation of extracellular matrix (ECM) formed mainly of collagen and fibronectin. Persistent deregulated IL-6 synthesis causes the development of various diseases. This study aim to investigate interleukin 6 (IL-6) serum level and gene polymorphism in a sample of Egyptian patients having keloid. This study was carried out on 90 subjects; 60 patients with keloid, and 30 age and sex matched apparently healthy control. All subjects underwent full history taking, clinical examinations, weight and length measuring to calculate BMI, dermatological examination, analysis of IL6-572 gene polymorphism using REFLP- PCR and IL-6 serum level using ELISA.IL-6 serum levels were significantly higher in keloid patients than control group (75.54±39.18) vs (19.17±6.06), (p <0.001). The higher serum levels of IL-6 were associated with GG genotype (104.84±19.12) followed by CG (57.64±35.38) genotype (P<0.001). GG genotype was significantly higher in keloid patients and increased the risk for keloid development by nearly14 folds (p<0.001, OR (95%CI) =13.81). CG genotype was significantly observed in keloid patients and increased the risk for keloid development by about 4 times (p=0.010, OR (95%CI) =4.27). G Allele significantly increased the risk for keloid development by about 5 folds (P <0.001 OR =5.11). In conclusion, there was a great association between IL-6 572 gene polymorphism and its serum level in patients with keloid specifically who have family history.

Keywords

Interleukin Keloid Polymorphism PCR Collagen.

Abdu Allah, A. M. K., Mohammed, K. I., Farag, A. G. A., Hagag, M. M., Essam, M., & Tayel, N. R. (2019). Interleukin-6 serum level and gene polymorphism in keloid patients. Cellular and Molecular Biology, 65(5), 43–48. https://doi.org/10.14715/cmb/2019.65.5.7

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References

References
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McLoughlin, R.M., Hurst, S.M., Nowell, M.A., Harris, D.A., Horiuchi, S., Morgan, L.W., et al. Differential regulation of neutrophil-activating chemokines by IL-6 and its soluble receptor isoforms. The Journal of Immunology, 2004; 172(9), pp.5676-5683.
Akdis, M., Burgler, S., Crameri, R., Eiwegger, T., Fujita, H., Gomez, E.,et al. Interleukins, from 1 to 37, and interferon-Î³: receptors, functions, and roles in diseases. Journal of allergy and clinical immunology, 2011; 127(3), pp.701-721.
Yao X, Cui X, Wu X, Xu P, Zhu W, Chen X, et al.Tumor suppressive role of miR-1224-5p in keloid proliferation, apoptosis and invasion via the TGFbeta1/Smad3 signaling pathway. Biochem Biophys Res Commun 2018;495:713–720.
Kendrick, M. Why being "overweight” means you live longer: The way scientists twist the facts. Independent, 2015.
Mengjiao Wang, Liqing Chen, Wei Huang, Mingji Jin, Qiming Wang, Zhonggao Gao .,et al.Improving the anti-keloid outcomes through liposomes loading paclitaxel–cholesterol complexes. International Journal of Nanomedicine 2019:14 1385–1400
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Shang T, Yao B, Gao D, Xie J, Fu X, Huang S. A.novel model of humanised keloid scarring in mice. Int Wound J 2018;15:90–94.
Hirano, T., Yasukawa, K., Harada, H., Taga, T., Watanabe, Y., Matsuda, T et al. Complementary DNA for a novel human interleukin (BSF-2) that induces B lymphocytes to produce immunoglobulin. Nature, 1986; 324, 73–76.
Fujiwara, M., Muragaki, Y. and Ooshima, A. Keloid"derived fibroblasts show increased secretion of factors involved in collagen turnover and depend on matrix metalloproteinase for migration. British journal of dermatology, 2005; 153(2), pp.295-300.
Marneros, A.G., Norris, J.E., Olsen, B.R. and Reichenberger, E. Clinical genetics of familial keloids. Archives of dermatology, 2001; 137(11), pp.1429-1434.
Alexander G. Marneros; James E. C. Norris, MD; Bjorn R. Olsen, MD, PhD; et alErnst Reichenberger, PhD. Author Affiliations Article Information Arch Dermatol. 2001; 137(11): 1429-1434.
Tae Hwan Park, Chan Woo Kim, Jin Sik Choi, Yun Joo Park, Yosep Chong, Min Ji Park, and Yuri Cho. PARP1 Inhibition as a Novel Therapeutic Target for Keloid Disease. ADVANCES IN WOUND CARE, 2019; 00, 00 by Mary Ann Liebert, Inc
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Zhu, X.J., Li, W.Z., Li, H., Fu, C.Q. and Liu, J., Association of interleukin-6 gene polymorphisms and circulating levels with keloid scars in a Chinese Han population. Genet Mol Res, 2017; 16, p.16029110.
Li, Y.Y., Zhou, C.W., Xu, J., Qian, Y. and Wang, X.M., Interleukin-6 C-572G gene polymorphism and coronary artery disease in Asian: a meta-analysis of 2511 subjects. International journal of clinical and experimental medicine, 2015; 8(6), p.8995.
Quong WL, Kozai Y, Ogawa R. A case of keloids complicated by castleman's disease: interleukin-6 as a keloid risk factor. Plast Reconstr Surg Global Open 2017;5:e1336.
Naka, T., Nishimoto, N. and Kishimoto, T., The paradigm of IL-6: from basic science to medicine. Arthritis Research & Therapy, 2002; 4(3), p.S233.
Ara, T. and DeClerck, Y.A., Interleukin-6 in bone metastasis and cancer progression. European journal of cancer, 2010; 46(7), pp.1223-1231.
Zhao B, Guan H, Liu JQ, Zheng Z, Zhou Q, Zhang J, et al. Hypoxia drives the transition of humandermal fibroblasts to a myofibroblast-like phenotype via the TGF-beta1/Smad3 pathway. Int J Mol Med 2017;39:153–159.
Tosa, M., Watanabe, A. and Ghazizadeh, M., IL-6 Polymorphism and Susceptibility to Keloid Formation in a Japanese Population. The Journal of investigative dermatology, 2016; 136(5), p.1069.
Cherel M, Campion L, Bezieau S, Campone M, Charrier J, Gaschet J.,et al. Molecular screening of interleukin-6 gene promoter and influence of -174G/C polymorphism on breast cancer. Cytokine. 2009; 47: 214-223
Yu, X, Li, Z, Chan, MT, Wu, WK. microRNA deregulation in keloids: an opportunity for clinical intervention? Cell Prolif. 2015; 48: 626– 630.

References

Vrijman, C., Van Drooge, A.M., Limpens, J., Bos, J.D., Van Der Veen, J.P.W., Spuls, P.I., et al. Laser and intense pulsed light therapy for the treatment of hypertrophic scars: a systematic review. British Journal of Dermatology, 2011; 165(5), pp.934-942.

Kose, O., Stewart, J., Waseem, A., Lalli, A. and Fortune, F. Expression of cytokeratins , adhesion and activation molecules in oral ulcers of Behçet's disease. Clinical and Experimental Dermatology: Experimental dermatology, 2008; 33(1), pp.62-69.

McLoughlin, R.M., Hurst, S.M., Nowell, M.A., Harris, D.A., Horiuchi, S., Morgan, L.W., et al. Differential regulation of neutrophil-activating chemokines by IL-6 and its soluble receptor isoforms. The Journal of Immunology, 2004; 172(9), pp.5676-5683.

Akdis, M., Burgler, S., Crameri, R., Eiwegger, T., Fujita, H., Gomez, E.,et al. Interleukins, from 1 to 37, and interferon-Î³: receptors, functions, and roles in diseases. Journal of allergy and clinical immunology, 2011; 127(3), pp.701-721.

Yao X, Cui X, Wu X, Xu P, Zhu W, Chen X, et al.Tumor suppressive role of miR-1224-5p in keloid proliferation, apoptosis and invasion via the TGFbeta1/Smad3 signaling pathway. Biochem Biophys Res Commun 2018;495:713–720.

Kendrick, M. Why being "overweight” means you live longer: The way scientists twist the facts. Independent, 2015.

Mengjiao Wang, Liqing Chen, Wei Huang, Mingji Jin, Qiming Wang, Zhonggao Gao .,et al.Improving the anti-keloid outcomes through liposomes loading paclitaxel–cholesterol complexes. International Journal of Nanomedicine 2019:14 1385–1400

Gauglitz, G.G., Korting, H.C., Pavicic, T., Ruzicka, T. and Jeschke, M.G. Hypertrophic scarring and keloids: pathomechanisms and current and emerging treatment strategies. Molecular medicine, 2011; 17(1), p.113.

Shang T, Yao B, Gao D, Xie J, Fu X, Huang S. A.novel model of humanised keloid scarring in mice. Int Wound J 2018;15:90–94.

Hirano, T., Yasukawa, K., Harada, H., Taga, T., Watanabe, Y., Matsuda, T et al. Complementary DNA for a novel human interleukin (BSF-2) that induces B lymphocytes to produce immunoglobulin. Nature, 1986; 324, 73–76.

Fujiwara, M., Muragaki, Y. and Ooshima, A. Keloid"derived fibroblasts show increased secretion of factors involved in collagen turnover and depend on matrix metalloproteinase for migration. British journal of dermatology, 2005; 153(2), pp.295-300.

Marneros, A.G., Norris, J.E., Olsen, B.R. and Reichenberger, E. Clinical genetics of familial keloids. Archives of dermatology, 2001; 137(11), pp.1429-1434.

Alexander G. Marneros; James E. C. Norris, MD; Bjorn R. Olsen, MD, PhD; et alErnst Reichenberger, PhD. Author Affiliations Article Information Arch Dermatol. 2001; 137(11): 1429-1434.

Tae Hwan Park, Chan Woo Kim, Jin Sik Choi, Yun Joo Park, Yosep Chong, Min Ji Park, and Yuri Cho. PARP1 Inhibition as a Novel Therapeutic Target for Keloid Disease. ADVANCES IN WOUND CARE, 2019; 00, 00 by Mary Ann Liebert, Inc

Nouri, K., Alster, T.S. and Ballard, C.J., (2009). Laser revision of scars. Laser revision of scars. Available at: http://www. emedicine. com/derm/topic519htm. Accessed February, 23.

Ketchum, L.D., Cohen, L.K. and Masifrs, F.W., Hypertrophic scars and keloids a collective review. Plastic and reconstructive surgery, 1974; 53(2), pp.140-154.

Zhu, X.J., Li, W.Z., Li, H., Fu, C.Q. and Liu, J., Association of interleukin-6 gene polymorphisms and circulating levels with keloid scars in a Chinese Han population. Genet Mol Res, 2017; 16, p.16029110.

Li, Y.Y., Zhou, C.W., Xu, J., Qian, Y. and Wang, X.M., Interleukin-6 C-572G gene polymorphism and coronary artery disease in Asian: a meta-analysis of 2511 subjects. International journal of clinical and experimental medicine, 2015; 8(6), p.8995.

Quong WL, Kozai Y, Ogawa R. A case of keloids complicated by castleman's disease: interleukin-6 as a keloid risk factor. Plast Reconstr Surg Global Open 2017;5:e1336.

Naka, T., Nishimoto, N. and Kishimoto, T., The paradigm of IL-6: from basic science to medicine. Arthritis Research & Therapy, 2002; 4(3), p.S233.

Ara, T. and DeClerck, Y.A., Interleukin-6 in bone metastasis and cancer progression. European journal of cancer, 2010; 46(7), pp.1223-1231.

Zhao B, Guan H, Liu JQ, Zheng Z, Zhou Q, Zhang J, et al. Hypoxia drives the transition of humandermal fibroblasts to a myofibroblast-like phenotype via the TGF-beta1/Smad3 pathway. Int J Mol Med 2017;39:153–159.

Tosa, M., Watanabe, A. and Ghazizadeh, M., IL-6 Polymorphism and Susceptibility to Keloid Formation in a Japanese Population. The Journal of investigative dermatology, 2016; 136(5), p.1069.

Cherel M, Campion L, Bezieau S, Campone M, Charrier J, Gaschet J.,et al. Molecular screening of interleukin-6 gene promoter and influence of -174G/C polymorphism on breast cancer. Cytokine. 2009; 47: 214-223

Yu, X, Li, Z, Chan, MT, Wu, WK. microRNA deregulation in keloids: an opportunity for clinical intervention? Cell Prolif. 2015; 48: 626– 630.

Author biographies is not available.