Chemoprevention by cyclooxygenase-2 inhibition reduces immature myeloid suppressor cell expansion

James E Talmadge, Keith C. Hood, Lori C. Zobel, Laura R. Shafer, Melissa Coles, Bela Toth

Research output: Contribution to journalArticle

95 Citations (Scopus)

Abstract

Selective inhibitors of cyclooxygenase-2 (COX-2) enzyme activity have shown chemopreventive activity in carcinogen-induced and transgenic rodent tumor models and clinically for colon cancer. However, the mechanism(s) by which COX-2 inhibitors reduce carcinogenesis remains controversial. We report herein that administration of the selective COX-2 inhibitor, celecoxib, significantly reduces the number of Gr1+CD11b+ immature myeloid suppressor cells (IMSCs) during chemoprevention of 1,2-dimethylhydrazine diHCl-(1,2-DMH-) induction of large intestinal tumors in Swiss mice. Celecoxib administration also increased splenic lymphatic number and tumor infiltration by lymphocytes. The 1,2-DMH induction of large intestinal tumors was associated with a four-fold increase in IMSCs, and a decrease in splenic T cell number and function. Concordant with the changes in the IMSC frequency, messenger ribonucleic acid (mRNA) levels of inducible nitric oxide synthase (NOS-2) and arginase (Arg) were increased in the spleen of the tumor-bearing mice and normalized by celecoxib administration. In addition to delaying tumor induction, reducing tumor number, and increasing lymphocyte infiltration of tumors, celecoxib therapy reversed CD4+ T cell loss, decreased IMSC numbers and increased mRNA levels of NOS-2 and Arg in the spleen. In summary, our results suggest that celecoxib chemoprevention of autochthonous intestinal tumors can regulate IMSCs and CD4+ T cell numbers.

Original languageEnglish (US)
Pages (from-to)140-151
Number of pages12
JournalInternational Immunopharmacology
Volume7
Issue number2
DOIs
StatePublished - Feb 1 2007

Fingerprint

Celecoxib
Chemoprevention
Myeloid Cells
Cyclooxygenase 2
Neoplasms
Cyclooxygenase 2 Inhibitors
Dimenhydrinate
Arginase
Cell Count
T-Lymphocytes
Spleen
RNA
1,2-Dimethylhydrazine
Lymphocyte Count
Nitric Oxide Synthase Type II
Carcinogens
Colonic Neoplasms
Rodentia
Carcinogenesis
Lymphocytes

Keywords

  • Carcinogenesis
  • Celecoxib
  • Chemoprevention
  • Dendritic cell
  • Immature myeloid suppressor cell

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology

Cite this

Chemoprevention by cyclooxygenase-2 inhibition reduces immature myeloid suppressor cell expansion. / Talmadge, James E; Hood, Keith C.; Zobel, Lori C.; Shafer, Laura R.; Coles, Melissa; Toth, Bela.

In: International Immunopharmacology, Vol. 7, No. 2, 01.02.2007, p. 140-151.

Research output: Contribution to journalArticle

Talmadge, James E ; Hood, Keith C. ; Zobel, Lori C. ; Shafer, Laura R. ; Coles, Melissa ; Toth, Bela. / Chemoprevention by cyclooxygenase-2 inhibition reduces immature myeloid suppressor cell expansion. In: International Immunopharmacology. 2007 ; Vol. 7, No. 2. pp. 140-151.
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