Navigation Links
Imiquimod, an immune response modifier, is dependent on the OGF-OGFr signaling pathway
Date:7/24/2008

Researchers at The Pennsylvania State University College of Medicine, Hershey, Pennsylvania have discovered that the efficacy of imiquimod, a clinically important immune response modifier with potent antiviral and antitumor activity, is dependent on the Opioid Growth Factor (OGF)-OGF receptor (OGFr) axis for its action. This discovery, reported in the August 08 issue of Experimental Biology and Medicine, provides new insights into a widely used drug that may lead to development of new agents that will enhance effectiveness and attenuate side-effects.

Imiquimod and resiquimod are imidazoquinoline compounds. Imiquimod (Aldara, R-837, S26308), the best characterized and most widely used, is highly efficacious in the treatment of external genital and anal warts, basal cell carcinoma, actinic keratoses, Kaposi's sarcoma, chronic hepatitis C infection, and intraepithelial carcinoma. Therefore, the underlying mechanism of imiquimod action is of clinical importance. Imiquimod has been reported to be a toll-like receptor-7 agonist, and its anti-tumor effect exerted by modification of the immune response and stimulation of apoptosis. The mechanism of imiquimod on cell proliferation is unclear.

The research team, led by Dr. Ian S. Zagon, Distinguished University Professor, and Dr. Patricia J. McLaughlin, Professor, along with a pre-doctoral student Renee N. Donahue, in the Department of Neural & Behavioral Sciences and collaborator Moshe Rogosnitzky of MedInsight explored mechanisms responsible for the remarkable clinical action of this class of drugs. Specifically, using tissue culture models, the investigators found that imidazoquinolines upregulate OGFr which in turn stimulates the interaction of the OGF-OGFr axis. This native, tonically active inhibitory pathway is known to regulate cell proliferation by modulating cyclin dependent kinase inhibitors, resulting in a retardation of cells at the G1-S interface of the cell cycle. Neutralization of OGF or knockdown of OGFr by siRNA technology eliminated the inhibitory effects of imidazoquinolines on cell replication. "Thus our data," Dr. Zagon said, "brings a paradigm shift to our thinking about a drug widely used in the clinics. Rather than imiquimod activity being mediated by induction of various cytokines, including interferon (IFN)-α, IFN-γ, tumor necrosis factor-α (TNFα) interleukin (IL)-1α, and IL-12 as currently thought, an entirely new pathway - native to body chemistry - has been discovered to regulate cell proliferation by imidazoquinolines." Co-author, Moshe Rogosnitzky adds: "The elucidation of imiquimod's immune-independent mechanism of action in cancer also creates exciting new therapeutic possibilities for a number of non-cancer conditions, and these are now being further explored. Such studies could lead to new off-label applications for imiquimod as well as development of imiquimod analogues and unique combination therapies." Dr. Steven R. Goodman, Editor-in-Chief of Experimental Biology and Medicine stated "Through decades of elegant and ground-breaking work, Zagon and colleagues have identified the role of met-enkephalin (the opioid growth factor OGF) and the OGF receptor in regulating cell proliferation. The current study demonstrates that the mechanism of imidazoquinoline activity is via OGF and OGFr which will have a profound impact on its use as a therapeutic for cancer and many other non-cancerous disorders."


'/>"/>

Contact: Dr. Ian S. Zagon
isz1@psu.edu
717-531-8650
Society for Experimental Biology and Medicine
Source:Eurekalert

112

GOOD

Related biology news :

1. Viral recombination another way HIV fools the immune system
2. Video released of rapid Alzheimers improvement after new immune-based treatment
3. Researchers hack final part of the immune system code
4. Control switches found for immune cells that fight cancer, viral infection
5. A single mechanism for hypertension, insulin resistance and immune suppression
6. Pitt receives $2.5 million to simulate and analyze brain, immune system activity
7. New findings on immune system in amphibians
8. UCLA researchers develop new PET scanning probe that will allowing monitoring of the immune system
9. Retraining immune cells to kill tumors
10. Sugar linkage could lead to better treatment for autoimmune diseases
11. Effective cancer immune therapy through order in the blood vessels
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:11/21/2016)... Nov. 21, 2016   Neurotechnology , a ... technologies, today announced that the MegaMatcher On Card ... submitted for the NIST Minutiae Interoperability Exchange ... the mandatory steps of the evaluation protocol. ... continuing test of fingerprint templates used to establish ...
(Date:11/15/2016)... Md. , Nov. 15, 2016  Synthetic ... company developing therapeutics focused on the gut microbiome, ... offering of 25,000,000 shares of its common stock ... common stock at a price to the public ... proceeds to Synthetic Biologics from the offering, excluding ...
(Date:6/22/2016)... American College of Medical Genetics and Genomics was once again ... of the fastest-growing trade shows during the Fastest 50 Awards ... Las Vegas . Winners are ... of the following categories: net square feet of paid exhibit ... 2015 ACMG Annual Meeting was ranked 23 out of 50 ...
Breaking Biology News(10 mins):
(Date:12/9/2016)... ... 2016 , ... DuPont Industrial Biosciences (DuPont) and Archer Daniels ... Award from Platts Global Energy for their platform technology to produce a ... the 18th Platts Global Energy Awards, held in New York on Thursday, Dec. 8. ...
(Date:12/9/2016)... 2016 The research report by ... in the  Global Label-Free Array Systems Market  accounted for ... 2015. Players such as Biacore, Agilent Technologies, ForteBio, Molecular ... the global market due to their unmatched product portfolio ... upgrades and timely product launches are expected to be ...
(Date:12/9/2016)... China Cord Blood Corporation (NYSE: CO ... leading provider of cord blood collection, laboratory testing, hematopoietic stem ... results of its 2016 Annual General Meeting, which was held ... China . At the Annual General ... KPMG Huazhen LLP as the independent auditors of the Company ...
(Date:12/9/2016)... , December 9, 2016 According to a ... (Primer, Probe, Custom, Predesigned, Reagent Equipment), Application (Research, PCR, Gene, DNA, ... 2021" published by MarketsandMarkets, the global market is expected to reach ... at a CAGR of 10.6% during the forecast period. ... ...
Breaking Biology Technology: