Current and Future Molecular Mechanism in Inflammation and Arthritis

  • Received : 2020.01.24
  • Accepted : 2020.05.28
  • Published : 2020.06.30


Inflammation is an immune response of the human body but excessive inflammation is taken as a major factor in the development of many diseases including autoimmune disorders, cancer and nerve disorders etc. In this regards the need is to suppress the inflammatory response. Suppression of extra or imperfect inflammatory response is not a big deal provided there is an exact knowledge of particular target in the body. Recent advancements in Pharmacological aspect made the therapy with improved outcomes in number of patients. Anticytokine therapy might be one of the important and novel approaches for inflammation and Arthritis. This can be achieved only when we go through the pathophysiology of expression and identification of mediators. Let's take an example of cytokine like interleukins (IL), chemokines, interferons (INF), tumor necrosis factors (TNF-α), growth factors, and colony stimulating factors) release pathway which is a major signalling protein in inflammatory response. In the present study we have reviewed the recent pharmacological therapeutic advancement, inflammatory mediators, receptors, and major signalling pathways. Such information will not only provide the idea about the mechanism of action of Pharmaceuticals and molecular targets but also it provides a new aspect for drug designing and new corrective approaches in existing clinical medicines. This study will be a source of good information for the researchers working in the area of drug designing and molecular Pharmacology especially in anti-inflammatory and anti arthritic medicines for target based therapy.


  1. Chen L, Deng H, Cui H, Fang J, Zuo Z, Deng J, et al. Inflammatory Responses and Inflammation-Associated Diseases in Organs. Oncotarget. 2018;9(6):7204-7218.
  2. Korniluk A, Koper O, Kemona H, Dymicka-Piekar-ska D. From inflammation to cancer. Ir J Med Sci. 2017;186(1):57-62.
  3. Gavrila BI, Ciofu C, Stoica V. Biomarkers in Rheumatoid Arthritis, what is new? J Med Life. 2016;9(2):144-148.
  4. Burmester GR, Pope JE. Novel Treatment Strategies in Rheumatoid Arthritis. Lancet. 2017;389(10086):2338-2348.
  5. Guo Q, Wang Y, Xu D, Nossent J, Pavlos NJ, Xu J. Rheumatoid Arthritis: Pathological Mechanisms and Modern Pharmacologic Therapies. Bone Res. 2018;6(15):1-14.
  6. Brown PM, Pratt AG, Isaacs JD. Mechanism of Action of Methotrexate in Rheumatoid Arthritis, and the Search for Biomarkers. Nat Rev Rheumatol. 2016;12(12):731-742.
  7. Tasneem S, Liu B, Li B, Choudhary MI, Wang W. Molecular Pharmacology of Inflammation: Medicinal Plants as Anti-Inflammatory Agents. Pharmacol Res. 2019;139(2019):126-140.
  8. Zhang JM, An J. Cytokines, Inflammation and Pain. Int Anesthesiol Clin. 2007;45(2):27-37
  9. Turner MD, Nedjai B, Hurst T, Pennington DJ. Cytokines and Chemokines: At the Crossroads of Cell Signalling and Inflammatory Disease. Biochim Biophys Acta. 2014;1843(11):2563-2582.
  10. Kindt TJ, Goldsby RA, Osborne BA. Kuby Immunology. 6th ed. New York: Freeman press; 2007.
  11. Hammaker D, Sweeney S, Firestein G. Signal transduction networks in rheumatoid arthritis. Ann Rheum Dis. 2003;62(Suppl 2):ii86-ii89.
  12. Seetharaman R, Mora AL, Nabozny G, Boothby M, Chen J. Essential Role of T Cell NF-kappa B Activation in Collagen-Induced Arthritis. J Immunol. 1999;163(3):1577-83.
  13. Wu Y, Antony S, Meitzler JL, Doroshow JH. Molecular mechanisms underlying chronic inflammation-associated cancers. Cancer Lett. 2014;345(2):164-173.
  14. Fitzgerald KA, Palsson-McDermott EM, Bowie AG, Jefferies CA, Mansell AS, Brady G, et al. Mal (MyD88-adapter-like) is Required for Toll-like receptor-4 Signal Transduction. Nature. 2001;413(6851):78-83.
  15. Kaplan MH. STAT signaling in inflammation. JAK-STAT. 2013;2(1);1-3.
  16. Yu H, Pardoll D, Jove R. STATs in Cancer Inflammation and Immunity: A Leading Role for STAT3. Nat Rev Cancer. 2009;9(11):798-809.
  17. Rawlings JS, Rosler KM, Harrison DA. The JAK/STAT signaling pathway. J Cell Sci. 2004;117(8):1281-1283.
  18. Seif F, Khosmirsafa M, Aazami H, Mohsenzadegan M, Sedighi G, Bahar M. The Role of JAK-STAT Signaling Pathway and Its Regulators in the Fate of T Helper Cells. Cell Commun Signal. 2017;15(1):23.
  19. Kawasaki T, Kawai T. Toll-Like Receptor Signaling Pathways. Front Immunol. 2014;5(461):1-8.
  20. Takeda K, Akira S. Toll-like Receptors. Curr Protoc Immunol. 2015;109:14.12.1-14.12.10.
  21. Takeda K, Kaisho T, Akira S. Toll-like Receptors. Annu Rev Immunol. 2003;21:335-76.
  22. Kaisho T, Akira S. Toll-like Receptor Function and Signaling. J Allergy Clin Immunol. 2006;117(5):979-87.
  23. Liu T, Zhang L, Joo D, Sun SC. NF-${\kappa}B$ Signaling in Inflammation. Signal Transduct Target Ther. 2017;2:17023.
  24. Soares-Silva M, Diniz FF, Gomes GN, Bahia D. The Mitogen-Activated Protein Kinase (MAPK) Pathway: Role in Immune Evasion by Trypanosomatids. Front Microbiol. 2016;7(183):1-9.
  25. Rawlings JS, Rosler KM, Harrison DA. The JAK/STAT signaling pathway. J Cell Sci. 2004;117(8):1281-1283.
  26. Harrison DA. The JAK/STAT Pathway. Cold Spring Harb Perspect Biol. 2012;4(3):a011205.
  27. Liu P, Cheng H, Roberts TM, Zhao JJ. Targeting the Phosphoinositide 3-kinase Pathway in Cancer. Nat Rev Drug Discov. 2009;8(8):627-44.
  28. Samuelsson B. Arachidonic Acid Metabolism: Role in Inflammation. Z Rheumatol. 1991;50(Suppl 1):3-6.
  29. Yang G, Chen L. An Update of Microsomal Prostaglandin E Synthase-1 and PGE2 Receptors in Cardiovascular Health and Diseases. Oxid Med Cell Longev. 2016;2016:5249086.
  30. Tallima H, Ridi RE. Arachidonic Acid: Physiological Roles and Potential Health Benefits -A Review. J Adv Res. 2017;11:33-41.
  31. Hanna VS, Hafez EAA. Synopsis of arachidonic acid metabolism: A review. J Adv Res. 2018;11:23-32.
  32. Poorani R, Bhatt AN, Dwarakanath BS, Das UN. COX-2, Aspirin and Metabolism of Arachidonic, Eicosapentaenoic and Docosahexaenoic Acids and Their Physiological and Clinical Significance. Eur J Pharmacol. 2016;15(785):116-132.
  33. Khanapure SP, Garvey DS, Janero DR, Letts LG. Eicosanoids in Inflammation: Biosynthesis, Pharmacology, and Therapeutic Frontiers. Curr Top Med Chem. 2007;7(3):311-40.
  34. Pannunzio A, Coluccia M. Cyclooxygenase-1 (COX-1) and COX-1 Inhibitors in Cancer: A Review of Oncology and Medicinal Chemistry Literature. Pharmaceuticals (Basel). 2018;11(4):101.
  35. Dennis EA, Norris PC. Eicosanoid Storm in Infection and Inflammation. Nat Rev Immunol. 2015;15(8):511-23.
  36. Ricciotti E, FitzGerald GA. Prostaglandins and Inflammation. Arterioscler Thromb Vasc Biol. 2011;31(5):986-1000.
  37. Smith WL, DeWitt DL, Garavito RM. Cyclooxygenases: Structural, Cellular, and Molecular Biology. Annu Rev Biochem. 2000;69:145-82.
  38. Requelme MA, Burra S, Kar R, Lampe P, Jiang JX. Mitogen-activated Protein Kinase (MAPK) Activated by Prostaglandin E2Phosphorylates Connexin 43 and Closes Osteocytic Hemichannels in Response to Continuous Flow Shear Stress. J Biol Chem. 2015;290(47):28321-8.
  39. Paul CN, Dennis EA. A Lipidomic Perspective on Inflammatory Macrophage Eicosanoid Signaling. Adv Biol Regul. 2014;54:99-110.
  40. Sirois P, Borgeat P. Pharmacology of the Leukotrienes. J Pharmacol. 1984;15(Suppl 1):53-68.