Matches in SemOpenAlex for { <https://semopenalex.org/work/W3080470610> ?p ?o ?g. }
- W3080470610 endingPage "114206" @default.
- W3080470610 startingPage "114206" @default.
- W3080470610 abstract "The Toll-like receptor 7 (TLR7) agonist imiquimod is an antitumor and antiviral drug used for the treatment of skin indications such as basal cell carcinoma, squamous cell carcinoma, and genital warts caused by the human papilloma virus. We show that imiquimod has TLR7-independent activity in which it directly inhibits phosphodiesterase (PDE), leading to cAMP increase, PKA-mediated CREB phosphorylation and subsequent CRE-dependent reporter transcription. The activation of the cAMP pathway by imiquimod is synergistically amplified by the β-adrenergic receptor agonist, isoproterenol. PDE inhibition is implied from cAMP measurements and CRE-reporter assays in intact RAW264.7 macrophages and HEK293T cells, and also directly demonstrated in-vitro using macrophages lysate. Moreover, molecular docking simulated the binding of imiquimod in the active site of PDE4B, enabled by the high molecular similarity between imiquimod and the adenine moiety of cAMP. As expected from the known anti-inflammatory role of cAMP inducers in stimulated macrophages, PDE inhibition by imiquimod results in reduced expression of the key pro-inflammatory cytokine TNFα, and enhanced expression of the key anti-inflammatory cytokine IL-10, compared to a different TLR7 agonist, loxoribine, as well as to the TLR4 agonist LPS. To conclude, our results indicate that the widely used inflammatory drug, imiquimod, is not only a TLR7 agonist, but also harbors a novel anti-inflammatory function as a PDE inhibitor. This off-target affects the desired therapeutic inflammatory activity of imiquimod and may be accountable for adverse side effects." @default.
- W3080470610 created "2020-09-01" @default.
- W3080470610 creator A5008989728 @default.
- W3080470610 creator A5009043846 @default.
- W3080470610 creator A5011818007 @default.
- W3080470610 creator A5016246409 @default.
- W3080470610 creator A5050736737 @default.
- W3080470610 creator A5088013444 @default.
- W3080470610 date "2020-12-01" @default.
- W3080470610 modified "2023-10-16" @default.
- W3080470610 title "A dual and conflicting role for imiquimod in inflammation: A TLR7 agonist and a cAMP phosphodiesterase inhibitor" @default.
- W3080470610 cites W1486943611 @default.
- W3080470610 cites W1529698986 @default.
- W3080470610 cites W1591311747 @default.
- W3080470610 cites W1610489281 @default.
- W3080470610 cites W1844264977 @default.
- W3080470610 cites W1897201563 @default.
- W3080470610 cites W1917777024 @default.
- W3080470610 cites W1963642761 @default.
- W3080470610 cites W1964718835 @default.
- W3080470610 cites W1968910000 @default.
- W3080470610 cites W1969885133 @default.
- W3080470610 cites W1971919168 @default.
- W3080470610 cites W1972776583 @default.
- W3080470610 cites W1974097445 @default.
- W3080470610 cites W1974912240 @default.
- W3080470610 cites W1977260711 @default.
- W3080470610 cites W1978506520 @default.
- W3080470610 cites W1978629444 @default.
- W3080470610 cites W1979065624 @default.
- W3080470610 cites W1988612173 @default.
- W3080470610 cites W1990591017 @default.
- W3080470610 cites W1993708083 @default.
- W3080470610 cites W1995461729 @default.
- W3080470610 cites W1995744610 @default.
- W3080470610 cites W1997845879 @default.
- W3080470610 cites W2012514476 @default.
- W3080470610 cites W2015908766 @default.
- W3080470610 cites W2018969070 @default.
- W3080470610 cites W2024918057 @default.
- W3080470610 cites W2026863303 @default.
- W3080470610 cites W2028242823 @default.
- W3080470610 cites W2031462278 @default.
- W3080470610 cites W2033355414 @default.
- W3080470610 cites W2033769733 @default.
- W3080470610 cites W2037629192 @default.
- W3080470610 cites W2037827983 @default.
- W3080470610 cites W2041168913 @default.
- W3080470610 cites W2042976701 @default.
- W3080470610 cites W2049210214 @default.
- W3080470610 cites W2054084735 @default.
- W3080470610 cites W2054947389 @default.
- W3080470610 cites W2059344017 @default.
- W3080470610 cites W2060381100 @default.
- W3080470610 cites W2063956233 @default.
- W3080470610 cites W2064815099 @default.
- W3080470610 cites W2067684973 @default.
- W3080470610 cites W2073433364 @default.
- W3080470610 cites W2083630984 @default.
- W3080470610 cites W2088359631 @default.
- W3080470610 cites W2089909459 @default.
- W3080470610 cites W2090989981 @default.
- W3080470610 cites W2100365601 @default.
- W3080470610 cites W2101175089 @default.
- W3080470610 cites W2108830583 @default.
- W3080470610 cites W2119408455 @default.
- W3080470610 cites W2121376700 @default.
- W3080470610 cites W2122319524 @default.
- W3080470610 cites W2128611559 @default.
- W3080470610 cites W2129319296 @default.
- W3080470610 cites W2130938511 @default.
- W3080470610 cites W2131332755 @default.
- W3080470610 cites W2131900949 @default.
- W3080470610 cites W2133096761 @default.
- W3080470610 cites W2134505828 @default.
- W3080470610 cites W2138260361 @default.
- W3080470610 cites W2145722383 @default.
- W3080470610 cites W2151460035 @default.
- W3080470610 cites W2153744286 @default.
- W3080470610 cites W2154558722 @default.
- W3080470610 cites W2159269771 @default.
- W3080470610 cites W2159365085 @default.
- W3080470610 cites W2166688499 @default.
- W3080470610 cites W2182198647 @default.
- W3080470610 cites W2209389920 @default.
- W3080470610 cites W2279143785 @default.
- W3080470610 cites W2316631291 @default.
- W3080470610 cites W2343100289 @default.
- W3080470610 cites W2515528675 @default.
- W3080470610 cites W2531502250 @default.
- W3080470610 cites W2588654653 @default.
- W3080470610 cites W2743105545 @default.
- W3080470610 cites W2769045700 @default.
- W3080470610 cites W2807588020 @default.
- W3080470610 cites W2897406695 @default.
- W3080470610 cites W2911079969 @default.
- W3080470610 cites W2938566986 @default.
- W3080470610 cites W2959234623 @default.