Inhibition of DNA synthesis in mouse epidermis by topical imiquimod is dependent on opioid receptors

Experimental Biology and Medicine

Volumn 235, Issue 11, 2010, Pages 1292-1299

  McLaughlin, Patricia J ^a   Rogosnitzky, Moshe ^b   Zagon, Ian S ^a  

^a PENN STATE COLLEGE OF MEDICINE   (United States)

^b MedInsight ^*  (Israel)

Author keywords

Bystander effect; Cell proliferation; Epithelium; Imiquimod; Immunity; Opioid; Opioid growth factor

Indexed keywords

GROWTH FACTOR; IMIQUIMOD; METENKEPHALIN; MORPHINE; NALOXONE; NALTREXONE; OPIATE AGONIST; OPIATE ANTAGONIST; OPIATE RECEPTOR; OPIOID GROWTH FACTOR; OPIOID GROWTH FACTOR RECEPTOR; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; APOPTOSIS; ARTICLE; C57BL 6 MOUSE; CELLULAR IMMUNITY; CONTROLLED STUDY; DNA SYNTHESIS; DNA SYNTHESIS INHIBITION; DRUG EFFECT; DRUG MECHANISM; EPIDERMIS; EPITHELIUM BASAL CELL; IMMUNE SYSTEM; IN VIVO STUDY; INHIBITION KINETICS; LOW DRUG DOSE; MITOSIS INHIBITION; MOUSE; NECROSIS; NOCICEPTION; NOCICEPTIVE STIMULATION; NONHUMAN; NUDE MOUSE; RECEPTOR UPREGULATION; SINGLE DRUG DOSE; SKIN CELL;

ADMINISTRATION, TOPICAL; AMINOQUINOLINES; ANIMALS; ANTINEOPLASTIC AGENTS; APOPTOSIS; CELL PROLIFERATION; DNA REPLICATION; EPIDERMIS; MICE; MICE, INBRED C57BL; MICE, NUDE; NALTREXONE; NARCOTIC ANTAGONISTS; NECROSIS; NUCLEIC ACID SYNTHESIS INHIBITORS; RECEPTORS, OPIOID; UP-REGULATION;

MUS; MUS MUSCULUS;

EID: 78049352618     PISSN: 15353702     EISSN: 15353699     Source Type: Journal    
DOI: 10.1258/ebm.2010.010203     Document Type: Article

References (25)

1. Miller RL, Gerster JF, Owens ML, Slade HB, Tomai MA. Imiquimod applied topically: a novel immune response modifier and new class of drug. Int J Immunopharmacol 1999;21:1-14
2. Tyring S, Conant M, Marini M, van der Meijden W, Washenik K. Imiquimod: an international update on therapeutic uses in dermatology. Int J Dermatol 2002;41:810-16 (Pubitemid 35422853)
3. Schon MP, Schon M. Imiquimod: mode of action. Br J Dermatol 2007;157:8-13
4. Huang SJ, Hijnen D, Murphy GF, Kupper TS, Calarese AW, Mollet IG, Schanbacher CF, Miller DM, Schmults CD, Clark RA. Imiquimod enhances IFN-g production and effector function of T cells infiltrating human squamous cell carcinomas of the skin. J Invest Dermatol 2009;129:2676-85
5. Schön M, Bong AP, Drewniok C, Herz J, Geilen CC, Reifenberger J, Benninghoff B, Slade HB, Gollnick H, Schön MP. Tumor-selective induction of apoptosis and the small-molecule immune response modifier imiquimod. J Natl Cancer Inst 2003;95:1138-49
6. De Giorgi V, Salvini C, Chiarugi A, Paglierani M, Maio V, Nicoletti P, Santucci M, Carli P, Massi D. In vivo characterization of the inflammatory infiltrate and apoptotic status in imiquimod-treated basal cell carcinoma. Int J Dermatol 2009;48:312-21
7. Urosevic M, Oberholzer PA, Maier T, Hafner J, Laine E, Slade H, Benninghoff B, Burg G, Dummer R. Imiquimod treatment induces expression of opioid growth factor receptor: a novel tumor antigen induced by interferon-a? Clin Cancer Res 2004;10:4959-70
8. Zagon IS, Verderame MF, McLaughlin PJ. The biology of the opioid growth factor receptor (OGFr). Brain Res Rev 2002;38:351-76
9. Cheng F, McLaughlin PJ, Verderame MF, Zagon IS. Dependence on nuclear localization signals of the opioid growth factor receptor in the regulation of cell proliferation. Exp Biol Med 2009;234:532-41
10. Donahue RN, McLaughlin PJ, Zagon IS. Cell proliferation of human ovarian cancer is regulated by the opioid growth factor-opioid growth factor receptor axis. Am J Physiol Regul Integr Comp Physiol 2009;296:R1716-25
11. Zagon IS, McLaughlin PJ. Opioids and the apoptotic pathway in human cancer cells. Neuropeptides 2003;37:79-8818
12. Zagon IS, McLaughlin PJ. Opioids and differentiation in human cancer cells. Neuropeptides 2005;39:495-505
13. Zagon IS, Rahn KA, McLaughlin PJ. Opioids and migration chemotaxis, invasion, and adhesion of human cancer cells. Neuropeptides 2007;41:441-52
14. Cheng F, McLaughlin PJ, Verderame MF, Zagon IS. The OGF-OGFr axis utilizes the p21 pathway to restrict progression of human pancreatic cancer. Mol Cancer 2007;7:5-17
15. Cheng F, McLaughlin PJ, Verderame MF, Zagon IS. The OGF-OGFr axis utilizes the p16INK4a and p21WAF1/CIP1 pathways to restrict normal cell proliferation. Mol Biol Cell 2009;20:319-27
16. Cheng F, Zagon IS, Verderame MF, McLaughlin PJ. The OGF-OGFr axis utilizes the p16 pathway to inhibit progression of human squamous cell carcinoma of the head and neck. Cancer Res 2077;67:10511-18
17. Zagon IS, Donahue RN, Rogosnitzky M, McLaughlin PJ. Imiquimod upregulates the opioid growth factor receptor to inhibit cell proliferation independent of immune function. Exp Biol Med 2008;233:968-79
18. Sidbury R, Neuschler N, Neuschler E, Sun P, Wang X, Miller R, Tomai M, Puscasiu E, Gugneja S, Paller AS. Topically applied imiquimod inhibits vascular tumor growth in vivo. J Invest Dermatol 2003;121:1205-9
19. Kang HY, Park TH, Jin SH. Imiquimod, a Toll-like receptor 7 agonist, inhibits melanogenesis and proliferation of human melanocytes. J Invest Dermatol 2009;129:243-6
20. Van der Fits L, Mourits S, Voerman JSA, Kant M, Boon L, Llaman JD, Cornelissen F, Mus A-M, Florencia E, Prens EP, Lubberts E. Imiquimod-induced psoriasis-like skin inflammation in mice is mediated via the IL-23/Il-17 axis. J Immunol 2009;182:5836-45
21. Wu JK, Siller G, Strutton G. Psoriasis induced by topical imiquimod. Australas J Dermatol 2004;45:47-50
22. Rajan N, Langtry JA. Generalized exacerbation of psoriasis associated with imiquimod cream treatment of superficial basal cell carcinoma. Clin Exp Dermatol 2006;31:140-1
23. Fanti PA, Dika E, Vaccari S, Miscial C, Varotti C. Generalized psoriasis induced by topical treatment of actinic keratosis with imiquimod. Int J Dermatol 2006;45:1464-5
24. 5]-enkephalin, and the ζ (zeta) opioid receptor are present in human and mouse skin and tonically act to inhibit DNA synthesis in the epidermis. J Invest Dermatol 1996;106:490-7
25. 5]-enkephalin, inhibits DNA synthesis during recornification of mouse tail skin. Cell Prolif 2000;33:63-73