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Chemoprevention by cyclooxygenase-2 inhibition reduces immature myeloid suppressor cell expansion
- Source :
- International Immunopharmacology. 7:140-151
- Publication Year :
- 2007
- Publisher :
- Elsevier BV, 2007.
-
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.
- Subjects :
- CD4-Positive T-Lymphocytes
medicine.medical_specialty
Myeloid
T cell
Immunology
Nitric Oxide Synthase Type II
Breast Neoplasms
Spleen
medicine.disease_cause
Mice
Adjuvants, Immunologic
Internal medicine
Intestinal Neoplasms
Concanavalin A
medicine
Animals
Anticarcinogenic Agents
Immunology and Allergy
RNA, Messenger
Antigen-presenting cell
Cell Proliferation
Pharmacology
Mice, Inbred BALB C
Sulfonamides
Arginase
Cyclooxygenase 2 Inhibitors
biology
Cell growth
Membrane Proteins
1,2-Dimethylhydrazine
Endocrinology
medicine.anatomical_structure
Celecoxib
Carcinogens
Cancer research
biology.protein
Pyrazoles
Female
Cyclooxygenase
Carcinogenesis
Neoplasm Transplantation
medicine.drug
Subjects
Details
- ISSN :
- 15675769
- Volume :
- 7
- Database :
- OpenAIRE
- Journal :
- International Immunopharmacology
- Accession number :
- edsair.doi.dedup.....614e8d6747bbd793626572c75cd94c28