Mechanistic insights into how  Tofacitinib attenuates rheumatoid arthritis:  Tofacitinib (brand name: Xeljanz), used to treat  rheumatoid/psoriatic arthritis and ulcerative colitis, increases IL-9 levels, augments proliferation of ILC2s (type 2 innate lymphoid cells) and regulatory T (Treg) cells, promotes resolution of inflammation, attenuates cartilage destruction, decreases bone loss, and inhibits pathological features associated with arthritis via up-regulation of its target genes, 5/August/2018, 1.29 am

Probiotic-based chemotherapy targeting cancer stem cells and immune-inhibitory receptors in advanced ovarian cancer and other metastatic cancers: A pharmaceutical mixture encompassing Olaparib, an FDA-approved poly (adenosine diphosphate-ribose) polymerase inhibitor, and probiotic Lactobacillus rhamnosus increases the expression of tumor suppressor genes, such as FASLG, KLF5,  p53, and TA-p73/p63, inhibits immune-inhibitory receptors/molecules, targets ovarian cancer stem cells, confers protection against chemoresistance and prolongs survival, via up-regulation of its target gene, 4/August/2019, 1.11 am
August 3, 2019
Mechanistic insights into how Alendronate attenuates Arthritis: Alendronate (brand name:  Fosamax), used to treat osteoarthritis and paget’s disease of bone, increases IL-9 levels, augments proliferation of ILC2s (type 2 innate lymphoid cells) and regulatory T (Treg) cells, promotes resolution of inflammation, attenuates cartilage destruction, decreases bone loss, and inhibits pathological features associated with arthritis, via up-regulation of its target genes, 10/August/2018, 6.02 pm
August 10, 2019
Show all

Introduction: What they say

A study from Department of Internal Medicine 3-Rheumatology and Immunology, Friedrich Alexander University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen, Germany shows that “Resolution of inflammation by interleukin-9-producing type 2 innate lymphoid cells.” This research paper was published, in the 17 July 2017 issue of the journal “Nature Medicine” [One of the best research journals in General Medicine with an I.Fs of 30.357], by Prof. Andreas Ramming, Rauber S and others.


What we say:

On the foundation of this interesting finding, Dr L Boominathan PhD, Director-cum-chief Scientist of GBMD, reports that:   Mechanistic insights into how  Tofacitinib attenuates rheumatoid arthritis:  Tofacitinib (brand name: Xeljanz), used to treat  rheumatoid/psoriatic arthritis and ulcerative colitis, increases IL-9 levels, augments proliferation of ILC2s (type 2 innate lymphoid cells) and regulatory T (Treg) cells, promotes resolution of inflammation, attenuates cartilage destruction, decreases bone loss, and inhibits pathological features associated with arthritis via up-regulation of its target genes

[easy_payment currency=”USD”]


From the significance of the study to Public health relevance:

Given that: (1) Rheumatoid arthritis (RA) has caused 49,000 deaths globally in 2010; and it is likely that death due to RA may increase in the coming years; (2) RA approximately affects between 0.5% to 1% of adults in the developing world; (3) between 5 and 50 per 100, 000 people develop RA each year; (3) Women are three to five times more affected by RA than men; (4) most of the drugs that are in use today, to treat RA, treats only the symptoms, not the root cause of the disease; (5) RA is characterized by chronic joint pains; and (6) the global economic cost spent in the treatment of RA is enormous, there is an urgent need to find: (i) molecular mechanisms and the components involved in bio-pathways leading to RA; (ii) a cheaper alternative to the existing expensive drugs; and (iii) a side-effect-free Natural product-based drug that alleviates not only Rheumatoid arthritis (RA) pain, but also cures RA.


What is known?

Prof.Andreas Ramming‘s research team has recently shown that: (1) interleukin (IL)-9-producing type 2 innate lymphoid cells (ILC2s) as mediators of chronic inflammation; (2) the lack of IL-9 production culminates in: (a) defective ILC2 proliferation and activation of regulatory T (Treg) cells; (b) arthritis; (c) excessive cartilage destruction; and (d) bone loss; (3) treatment with IL-9 results in a) resolution of inflammation; and b) protection of bone; and (4) increased numbers of IL-9+ILC2s in joints and the circulation of patients, in remission stage of rheumatoid arthritis, suggesting that IL-9-mediated ILC2 activation is a method of treatment for chronic inflammation, such as arthritis, as it promotes resolution of inflammation rather than suppression of inflammatory mediators.


From research findings to Therapeutic opportunity:

Earlier, a study from the Metroplex Clinical Research Center, Dallas, Texas 75231, USA published its research findings stating that “Placebo-controlled trial of tofacitinib monotherapy in rheumatoid arthritis.” This study was published, in the 9 Aug 2019 issue of of the prestigious journal N Engl J Med. (NEJM) (Impact factor: 79.258+),  by  Profs. Fleischmann R, Kanik KS, and others. This study suggests that tofacitinib, a Janus kinase (JAK3) inhibitor, attenuates and is efficacious in improving health conditions of patients with rheumatoid arthritisHowever, the precise mechanism of action of this drug remains largely unclear. 

The study presented here substantiates and supports the aforementioned studies claim by providing a detailed mechanistic insights into how tofacitinib may aid in attenuating rheumatoid/psoriatic  arthritis.

Tofacitinib, which is commonly used to rheumatoid/psoriatic arthritis and ulcerative colitis, by increasing the expression of its target gene, it may increase the expression of IL-9 and its down stream target genes (Figs. 1-2). Thereby, it may: (1) increase the proliferation of ILC2s cells; (2) promote activation of Treg cells; (3) promote resolution of inflammation; (4) suppress cartilage destruction; (5) inhibit bone loss and strengthen bone structure; and (6) inhibit arthritis progression (Figs 2-4).

Figure1. Mechanistic insights into how Tofacitinib increases IL-9 levels promotes proliferation/activation of ILC2s/Treg cells, enhances the resolution of inflammation, stifles cartilage destruction and inhibits bone loss.

Figure 2. The chemical structure Tofacitinib. Tofacitinib may attenuate inflammation, rheumatoid/psoriatic arthritis and ulcerative colitis through up-regulation of IL-9

Figure 3. While it has been shown that Tofacitinib attenuates rheumatoid/psoriatic arthritis, this study shows for the first time that Tofacitinib attenuates rheumatoid/psoriatic arthritisthrough up-regulation of IL-9.

Figure 4. While it has been shown that pharmacological activation of IL-9 producing type 2 innate lymphoid cells (ILC2s) attenuates inflammatory diseases, including rheumatoid arthritis, this study suggests for the first time that Tofacitinib attenuates rheumatoid/psoriatic arthritis through up-regulation of IL-9.

Together, this study suggests that a pharmacological mixture encompassing “tofacitinib or its analogs”, either alone or in combination with other drugs, will attenuate the progression of rheumatoid/psoriatic  arthritis. 


Details of the research findings:

Idea Proposed/Formulated (with experimental evidence) by: Dr L Boominathan Ph.D.

Terms & Conditions apply http://genomediscovery.org/registration/terms-and-conditions/

Amount: $ 500#

Undisclosed mechanistic information: How Tofacitinib increases IL-9 levels, activates ILC2 proliferation and regulatory T (Treg) cells, inhibits cartilage destruction, suppresses bone loss and improves arthritis.

# Research cooperation

For purchase and payment details, you may reach us at admin@genomediscovery.org


References:

Web: http://genomediscovery.org or http://newbioideas.com

Citation: Boominathan, L.,  Mechanistic insights into how  Tofacitinib attenuates rheumatoid arthritis:  Tofacitinib (brand name: Xeljanz), used to treat  rheumatoid/psoriatic arthritis and ulcerative colitis, increases IL-9 levels, augments proliferation of ILC2s (type 2 innate lymphoid cells) and regulatory T (Treg) cells, promotes resolution of inflammation, attenuates cartilage destruction, decreases bone loss, and inhibits pathological features associated with arthritis via up-regulation of its target genes, 5/August/2018, 1.29 am, Genome-2-Bio-Medicine Discovery center (GBMD), http://genomediscovery.org

Courtesy: When you cite us, kindly drop us a line at admin@genomediscovery.org

Comments are closed.