Effects of imiquimod treatment on TNF expression in two-step skin carcinogenesis model in mice.
Anna
A.
Chashchina1, 2*,
Svetlana
V.
Bozrova1, 2,
Ruslan
V.
Zvartsev2,
Thomas
Kammertoens3,
Victor
A.
Levitsky4, 5,
Sergei
A.
Nedospasov1, 2 and
Marina
S.
Drutskaya1, 2
-
1
Chair of Immunology, Biological Faculty, Lomonosov Moscow State University, Russia
-
2
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Russia
-
3
Institute of Immunology, Charité Campus Buch, Germany
-
4
Department of Oncology, The Johns Hopkins University School of Medicine, The Johns Hopkins University, United States
-
5
Discovery Oncology, Roche Glycart, Pharma Research and Early Development (pRED), Roche, Switzerland
Aldara, 5% imiquimod cream, is widely used in the clinic for treatment of virus-associated genital warts and several forms of skin cancer. There is evidence indicating a boost in the immune response against virus-infected or transformed cells following imiquimod application. Imiquimod has been initially characterized as an agonist of TLR7/8, however, most recent data suggest that it has a wider mode of action. In particular, it may be involved in regulating cAMP levels resulting in immunosuppression. We found that imiquimod dampens TNF production in both bone-marrow derived and peritoneal macrophages in response to LPS. Moreover, production of TNF is inhibited by imiquimod in vivo – in LPS/D-Gal hepatotoxicity model, as well as in LPS-induced septic shock. As TNF-mediated inflammation has been shown to support tumor formation in skin carcinogenesis, we wanted to assess effects of imiquimod treatment on inflammation during early stages of carcinogenesis. For this purpose, we performed two-step skin carcinogenesis experiments applying DMBA/TPA to the back skin of Balb/C mice followed by imiquimod treatment. Two weeks after DMBA application followed by six TPA applications, skin samples were harvested and expression profile of several proinflammatory cytokines was analyzed. We found that animals subjected to DMBA/TPA and then treated by imiquimod had significantly decreased levels of TNF and other pro-inflammatory cytokines compared with the controls. Taken together, our data indicate that imiquimod inhibits TNF production in several experimental models, including the two-step skin carcinogenesis, thereby providing a new insight into its mode of action in patients undergoing Aldara treatment.
Acknowledgements
This project was partially supported by RFBR grants 13-04-02052 and 11-04-91320.
Keywords:
imiquimod,
TNF,
Carcinogenesis,
Inflammation,
Macrophages
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Immune-mediated disease pathogenesis
Citation:
Chashchina
AA,
Bozrova
SV,
Zvartsev
RV,
Kammertoens
T,
Levitsky
VA,
Nedospasov
SA and
Drutskaya
MS
(2013). Effects of imiquimod treatment on TNF expression in two-step skin carcinogenesis model in mice..
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00579
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Received:
20 May 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Ms. Anna A Chashchina, Chair of Immunology, Biological Faculty, Lomonosov Moscow State University, Moscow, 119991, Russia, chashchina.anna@gmail.com