Mohamed Yousry, M., Abas Farag, E., Ibraheem Omar, A. (2023). Histological Study on the Possible Ameliorating Consequence of Blocking STAT-3 Pathway on Psoriasis Model in Adult Male Albino rat. test, 4(3), 92-118. doi: 10.21608/ejmr.2023.214067.1397
Marwa Mohamed Yousry; Eman Abas Farag; Abeer Ibraheem Omar. "Histological Study on the Possible Ameliorating Consequence of Blocking STAT-3 Pathway on Psoriasis Model in Adult Male Albino rat". test, 4, 3, 2023, 92-118. doi: 10.21608/ejmr.2023.214067.1397
Mohamed Yousry, M., Abas Farag, E., Ibraheem Omar, A. (2023). 'Histological Study on the Possible Ameliorating Consequence of Blocking STAT-3 Pathway on Psoriasis Model in Adult Male Albino rat', test, 4(3), pp. 92-118. doi: 10.21608/ejmr.2023.214067.1397
Mohamed Yousry, M., Abas Farag, E., Ibraheem Omar, A. Histological Study on the Possible Ameliorating Consequence of Blocking STAT-3 Pathway on Psoriasis Model in Adult Male Albino rat. test, 2023; 4(3): 92-118. doi: 10.21608/ejmr.2023.214067.1397

Histological Study on the Possible Ameliorating Consequence of Blocking STAT-3 Pathway on Psoriasis Model in Adult Male Albino rat

Egyptian Journal of Medical Research
Volume 4, Issue 3, July 2023, Pages 92-118    PDF (1.57 M)
Document Type: Original Article
DOI: 10.21608/ejmr.2023.214067.1397
Authors
Marwa Mohamed Yousry* 1; Eman Abas Farag1; Abeer Ibraheem Omar2
1Histology Department, Faculty of Medicine, Cairo University
2Histology Department, Faculty of Medicine, Cairo University
Abstract
Background: Psoriasis, autoimmune chronic inflammatory skin disease, affects 2-3% of population. It causes poor life-quality due to its disfiguring lesions and co-morbidities. Interleukin (IL)-23/T-helper (Th)-17 &IL-23/Th-22 axes activation, signal transducer and activator of transcription (STAT)-3 pathway stimulation and proinflammatory cytokines (IL-6, IL-17, IL-22 &TNF-α) overproduction are psoriasis main mechanisms. Psoriasis conventional treatment has many adverse effects as immunosuppression and hepatotoxicity with consequent lack of patients’ compliance. Aim of work: Evaluating the probable curative effect of blocking STAT-3 pathway using ochromycinone [an STA-21 (STAT-3 inhibitor)] on Imiquimod (IMQ)-induced psoriasis model in adult male albino rats.  Materials &Methods: 1 cm2 back skin was shaved in twenty-four adult male albino rats. They grouped into; control group [group-I], IMQ group [group-II, received 20mg/cm2 IMQ-5% topically on the shaved skin for 17 days] & IMQ/STA-21 group [group-III, given daily 3.5mg/kg ochromycinone intraperitoneal injection for 2 weeks]. Psoriasis Area &Severity Index (PASI)-scoring and biochemical, histological, immunohistochemical [for IL-23, STAT-3, Ki-67, connexin (Cx)-26 &vascular endothelial growth factor (VEGF)] and statistical studies were done. Results: IMQ produced psoriasis-like skin lesions (inflammation, epidermal proliferation & angiogenesis). However, the use of STA-21 marvelously ameliorated these lesions. Conclusion:  Topical IMQ provoked psoriasis-like lesions concerning gross, biochemical &histological features. These resulted from IL-23/Th-17 &IL-23/Th-22 axes activation, proinflammatory cytokines production that acted via STAT-3 pathway activation. The use of an STA-21 (STAT-3 inhibitor) as ochromycinone showed amazing improvement of these lesions. Thus, blocking STAT-3 might be a promising treatment for psoriasis instead of the traditional therapy with its marked side-effects.
Keywords
IMQ-induced psoriasis; IL-23; STAT-3; Ki-67; VEGF
References
  1. Springate DA, Parisi R, Kontopantelis E, Reeves D, Griffiths CE, Ashcroft DM. Incidence, prevalence and mortality of patients with psoriasis: a U.K. population-based cohort study. Br J Dermatol. 2017; 176:650-8. 
  2. Mitran MI, Mitran CI, Sârbu MI, Benea V, Tampa M, Georgescu SR. Therapeutic challenges in a case of psoriasis with nail onset. J. Mind Med. Sci. 2017; 4: 186-192.
  3. Tampa M, Sarbu MI, Mitran MI, Mitran CI, Matei C, Georgescu SR. The Pathophysiological Mechanisms and the Quest for Biomarkers in Psoriasis, a Stress-Related Skin Disease. Dis Markers. 2018; 2018:5823684.
  4. Sarbu MI, Tampa M, Sarbu AE, Georgescu SR. Sexual dysfunctions in psoriatic patients. J. Mind Med. Sci. 2014; 1: 19–27.
  5. Oliveira Mde F, Rocha Bde O, Duarte GV. Psoriasis: classical and emerging comorbidities. An Bras Dermatol. 2015; 90:9-20.
  6. Woo YR, Park CJ, Kang H, Kim JE. The Risk of Systemic Diseases in Those with Psoriasis and Psoriatic Arthritis: From Mechanisms to Clinic. Int J Mol Sci. 2020; 21:7041.
  7. Pithadia DJ, Reynolds KA, Lee EB, Wu JJ. Psoriasis-associated cutaneous pain: etiology, assessment, impact, and management. J Dermatolog Treat. 2019; 30:435-440.
  8. Chiricozzi A, Romanelli P, Volpe E, Borsellino G, Romanelli M. Scanning the Immunopathogenesis of Psoriasis. Int J Mol Sci. 2018; 19:179. 
  9. Lande R, Botti E, Jandus C, Dojcinovic D, Fanelli G, Conrad C, Chamilos G, Feldmeyer L, Marinari B, Chon S, Vence L, Riccieri V, Guillaume P, Navarini AA, Romero P, Costanzo A, Piccolella E, Gilliet M, Frasca L. The antimicrobial peptide LL37 is a T-cell autoantigen in psoriasis. Nat Commun. 2014; 5:5621.
  10. Krueger JG. An autoimmune "attack" on melanocytes triggers psoriasis and cellular hyperplasia. J Exp Med. 2015; 212:2186.
  11. Lande R, Gregorio J, Facchinetti V, Chatterjee B, Wang YH, Homey B, Cao W, Wang YH, Su B, Nestle FO, Zal T, Mellman I, Schröder JM, Liu YJ, Gilliet M. Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide. Nature. 2007; 449:564-9.
  12. Eberle FC, Brück J, Holstein J, Hirahara K, Ghoreschi K. Recent advances in understanding psoriasis. F1000Res. 2016; 5:F1000 Faculty Rev-770. 
  13. Fotiadou C, Lazaridou E, Sotiriou E, Ioannides D. Targeting IL-23 in psoriasis: current perspectives. Psoriasis (Auckl). 2018; 8:1-5.
  14. Georgescu SR, Sârbu MI, Matei C, Ilie MA, Caruntu C, Constantin C, Neagu M, Tampa M. Capsaicin: Friend or Foe in Skin Cancer and Other Related Malignancies? Nutrients. 2017; 9:1365.
  15. Monin L, Gaffen SL. Interleukin 17 Family Cytokines: Signaling Mechanisms, Biological Activities, and Therapeutic Implications. Cold Spring Harb Perspect Biol. 2018;10: a028522. 
  16. Giunta A, Ventura A, Chimenti MS, Bianchi L, Esposito M. Spotlight on ixekizumab for the treatment of moderate-to-severe plaque psoriasis: design, development, and use in therapy. Drug Des Devel Ther. 2017; 11:1643-51.
  17. Yang X, Zheng SG. Interleukin-22: a likely target for treatment of autoimmune diseases. Autoimmun Rev. 2014; 13:615-20.
  18. Luan C, Chen X, Hu Y, Hao Z, Osland JM, Chen X, Gerber SD, Chen M, Gu H, Yuan R. Overexpression and potential roles of NRIP1 in psoriasis. Oncotarget. 2016; 7:74236-46. 
  19. Winterfield L, Cather J, Cather J, Menter A. Changing paradigms in dermatology: nuclear hormone receptors. Clin Dermatol. 2003; 21:447-54.
  20. Pouplard C, Brenaut E, Horreau C, Barnetche T, Misery L, Richard MA, Aractingi S, Aubin F, Cribier B, Joly P, Jullien D, Le Maître M, Ortonne JP, Paul C. Risk of cancer in psoriasis: a systematic review and meta-analysis of epidemiological studies. J Eur Acad Dermatol Venereol. 2013; 27:36-46.
  21. Dogra S, Yadav S. Acitretin in psoriasis: an evolving scenario. Int J Dermatol. 2014; 53:525-38.
  22. Okasha EF, Bayomy NA, Abdelaziz EZ. Effect of Topical Application of Black Seed Oil on Imiquimod-Induced Psoriasis-like Lesions in the Thin Skin of Adult Male Albino Rats. Anat Rec (Hoboken). 2018; 301:166-174.
  23. Ahmad SF, Ansari MA, Nadeem A, Zoheir KMA, Bakheet SA, Alsaad AMS, Al-Shabanah OA, Attia SM. STA-21, a STAT-3 inhibitor, attenuates the development and progression of inflammation in collagen antibody-induced arthritis. Immunobiology. 2017; 222:206-17.
  24. Na Takuathung M, Wongnoppavich A, Panthong A, Khonsung P, Chiranthanut N, Soonthornchareonnon N, Sireeratawong S. Antipsoriatic Effects of Wannachawee Recipe on Imiquimod-Induced Psoriasis-Like Dermatitis in BALB/c Mice. Evid Based Complement Alternat Med. 2018; 2018:7931031. 
  25. El Agaty SM. Cardioprotective effect of vitamin D2 on isoproterenol-induced myocardial infarction in diabetic rats. Archives of Physiology and Biochemistry. 2019; 125:210-9
  26. Suvarna K, Layton C, Bancroft J. The hematoxylins and eosin, Immunohistochemical techniques & Transmission electron microscopy. In Bancroft's Theory and Practice of Histological Techniques (Eighth Edition), Elsevier,2019, pp: 126-38, 337-94, 434-75
  27. Li B, Tsoi LC, Swindell WR, Gudjonsson JE, Tejasvi T, Johnston A, Ding J, Stuart PE, Xing X, Kochkodan JJ, Voorhees JJ, Kang HM, Nair RP, Abecasis GR, Elder JT. Transcriptome analysis of psoriasis in a large case-control sample: RNA-seq provides insights into disease mechanisms. J Invest Dermatol. 2014; 134:1828-38. 
  28. Kim J, Krueger JG. The immunopathogenesis of psoriasis. Dermatol Clin. 2015; 33:13-23.
  29. Lowes MA, Suárez-Fariñas M, Krueger JG. Immunology of psoriasis. Annu Rev Immunol. 2014; 32:227-55. 
  30. Georgescu SR, Tampa M, Caruntu C, Sarbu MI, Mitran CI, Mitran MI, Matei C, Constantin C, Neagu M. Advances in Understanding the Immunological Pathways in Psoriasis. Int J Mol Sci. 2019; 20:739.
  31. Mohd Noor AA, Azlan M, Mohd Redzwan N. Orchestrated Cytokines Mediated by Biologics in Psoriasis and Its Mechanisms of Action. Biomedicines. 2022; 10:498.
  32. Baliwag J, Barnes DH, Johnston A. Cytokines in psoriasis. Cytokine. 2015; 73:342-50. 
  33. Smajlović A, Haverić A, Alić A, Hadžić M, Smajlović A, Mujezinović I, Lojo-Kadrić N, Ramić J, Elez-Burnjaković N, Haverić S, Pojskić L. Molecular and histopathological profiling of imiquimod induced dermatosis in Swiss Wistar rats: contribution to the rat model for novel anti-psoriasis treatments. Mol Biol Rep. 2021; 48:4295-303.
  34. Satake K, Amano T, Okamoto T. Low systemic exposure and calcemic effect of calcipotriol/betamethasone ointment in rats with imiquimod-induced psoriasis-like dermatitis. Eur J Pharmacol. 2018; 826:31-38. 
  35. Sun J, Zhao Y, Hu J. Curcumin inhibits imiquimod-induced psoriasis-like inflammation by inhibiting IL-1beta and IL-6 production in mice. PLoS One. 2013;8:e67078. 
  36. Na Takuathung M, Wongnoppavich A, Pitchakarn P, Panthong A, Khonsung P, Chiranthanut N, Soonthornchareonnon N, Sireeratawong S. Effects of Wannachawee Recipe with Antipsoriatic Activity on Suppressing Inflammatory Cytokine Production in HaCaT Human Keratinocytes. Evid Based Complement Alternat Med. 2017; 2017:5906539. 
  37. Shaker OG, Khairallah M, Rasheed HM, Abdel-Halim MR, Abuzeid OM, El Tawdi AM, El Hadidi HH, Ashmaui A. Antiangiogenic effect of methotrexate and PUVA on psoriasis. Cell Biochem Biophys. 2013; 67:735-42. 
  38. Rückert R, Asadullah K, Seifert M, Budagian VM, Arnold R, Trombotto C, Paus R, Bulfone-Paus S. Inhibition of keratinocyte apoptosis by IL-15: a new parameter in the pathogenesis of psoriasis? J Immunol. 2000; 165:2240-50. 
  39. Dwarampudi LP, Palaniswamy D, Nithyanantham M, Raghu PS. Antipsoriatic activity and cytotoxicity of ethanolic extract of Nigella sativa seeds. Pharmacogn Mag. 2012; 8:268-72. 
  40. Buerger C, Shirsath N, Lang V, Berard A, Diehl S, Kaufmann R, Boehncke WH, Wolf P. Inflammation dependent mTORC1 signaling interferes with the switch from keratinocyte proliferation to differentiation. PLoS One. 2017; 12:e0180853.
  41. O'Shaughnessy EM, Duffy W, Garcia-Vega L, Hussey K, Burden AD, Zamiri M, Martin PE. Dysregulation of Connexin Expression Plays a Pivotal Role in Psoriasis. Int J Mol Sci. 2021; 22:6060.
  42. Garcia-Vega L, O'Shaughnessy EM, Albuloushi A, Martin PE. Connexins and the Epithelial Tissue Barrier: A Focus on Connexin 26. Biology (Basel). 2021; 10:59.
  43. Hanlon MM, Rakovich T, Cunningham CC, Ansboro S, Veale DJ, Fearon U, McGarry T. STAT3 Mediates the Differential Effects of Oncostatin M and TNFα on RA Synovial Fibroblast and Endothelial Cell Function. Front Immunol. 2019; 10:2056.
  44. Dong J, Cheng XD, Zhang WD, Qin JJ. Recent Update on Development of Small-Molecule STAT3 Inhibitors for Cancer Therapy: From Phosphorylation Inhibition to Protein Degradation. J Med Chem. 2021; 64:8884-915.
  45. Johnson DE, O'Keefe RA, Grandis JR. Targeting the IL-6/JAK/STAT3 signalling axis in cancer. Nat Rev Clin Oncol. 2018; 15:234-48.
  46. Sgrignani J, Garofalo M, Matkovic M, Merulla J, Catapano CV, Cavalli A. Structural Biology of STAT3 and Its Implications for Anticancer Therapies Development. Int J Mol Sci. 2018; 19:1591. 
  47. Park JS, Kwok SK, Lim MA, Kim EK, Ryu JG, Kim SM, Oh HJ, Ju JH, Park SH, Kim HY, Cho ML. STA-21, a promising STAT-3 inhibitor that reciprocally regulates Th17 and Treg cells, inhibits osteoclastogenesis in mice and humans and alleviates autoimmune inflammation in an experimental model of rheumatoid arthritis. Arthritis Rheumatol. 2014; 66:918-29. 
  48. Song H, Wang R, Wang S, Lin J. A low-molecular-weight compound discovered through virtual database screening inhibits Stat3 function in breast cancer cells. Proc Natl Acad Sci U S A. 2005; 102:4700-5.
Statistics
Article View: 276
PDF Download: 173