Epinephrine promotes COX-2-dependent immune suppression in myeloid cells and cancer tissues

Ravikumar Muthuswamy, Nana J. Okada, Frank J. Jenkins, Kandace McGuire, Priscilla F. McAuliffe, Herbert J. Zeh, David L. Bartlett, Callen Wallace, Simon Watkins, Jill D. Henning, Dana H. Bovbjerg, Pawel Kalinski

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Activation of the sympathetic nervous system (e.g., due to stress) has been implicated in cancer progression and recurrence, but its cancer-promoting effects have been variable between different studies. Here, we report that although catecholamines, mediators of systemic sympathetic activity, display only weak immunosuppressive impact on their own, their combination with inflammatory signals leads to the induction of COX-2 and multiple COX-2-dependent suppressive factors in human myeloid cells and cancer tissues. Human macrophages exposed to epinephrine and TNFα, or macrophages generated in 6 day cultures in the presence of epinephrine, expressed high levels of COX-2, IDO and IL-10, and strongly suppressed both the proliferation and IFNγ production of CD8+ T cells. These suppressive effects of epinephrine were counteracted by celecoxib, a selective inhibitor of COX-2 activity, which inhibited the induction of immunosuppressive factors (including the elevated expression of COX-2 itself) and the ability of epinephrine-exposed macrophages to suppress CD8+ T cell responses. The activation of the COX-2/PGE2 system and COX-2-dependent suppressive events were also observed in ex vivo human breast and colon cancer explant cultures and were similarly counteracted by celecoxib. Our preliminary data also indicate elevated COX-2 expression in mammary tumors of chronic stress-exposed mice. The current demonstration of the interplay between inflammation and the induction of immunosuppressive factors by catecholamines suggest a contextual impact of stress, helping to explain variable results of epidemiologic studies of the link between sympathetic activity and cancer progression, and implicating COX-2 blockade as a potential means to mitigate stress-related immune suppression.

Original languageEnglish (US)
Pages (from-to)78-86
Number of pages9
JournalBrain, Behavior, and Immunity
Volume62
DOIs
StatePublished - May 1 2017
Externally publishedYes

Fingerprint

Celecoxib
Myeloid Cells
Epinephrine
Immunosuppressive Agents
Macrophages
Catecholamines
Neoplasms
Breast Neoplasms
T-Lymphocytes
Cyclooxygenase 2 Inhibitors
Sympathetic Nervous System
Dinoprostone
Interleukin-10
Colonic Neoplasms
Epidemiologic Studies
Inflammation
Recurrence

Keywords

  • Breast cancer
  • cAMP
  • Colon cancer
  • CTLs
  • Epinephrine
  • IDO
  • Immune suppression
  • Inflammation
  • Prostaglandins
  • Stress
  • Suppressive macrophages

ASJC Scopus subject areas

  • Immunology
  • Endocrine and Autonomic Systems
  • Behavioral Neuroscience

Cite this

Muthuswamy, R., Okada, N. J., Jenkins, F. J., McGuire, K., McAuliffe, P. F., Zeh, H. J., ... Kalinski, P. (2017). Epinephrine promotes COX-2-dependent immune suppression in myeloid cells and cancer tissues. Brain, Behavior, and Immunity, 62, 78-86. https://doi.org/10.1016/j.bbi.2017.02.008

Epinephrine promotes COX-2-dependent immune suppression in myeloid cells and cancer tissues. / Muthuswamy, Ravikumar; Okada, Nana J.; Jenkins, Frank J.; McGuire, Kandace; McAuliffe, Priscilla F.; Zeh, Herbert J.; Bartlett, David L.; Wallace, Callen; Watkins, Simon; Henning, Jill D.; Bovbjerg, Dana H.; Kalinski, Pawel.

In: Brain, Behavior, and Immunity, Vol. 62, 01.05.2017, p. 78-86.

Research output: Contribution to journalArticle

Muthuswamy, R, Okada, NJ, Jenkins, FJ, McGuire, K, McAuliffe, PF, Zeh, HJ, Bartlett, DL, Wallace, C, Watkins, S, Henning, JD, Bovbjerg, DH & Kalinski, P 2017, 'Epinephrine promotes COX-2-dependent immune suppression in myeloid cells and cancer tissues', Brain, Behavior, and Immunity, vol. 62, pp. 78-86. https://doi.org/10.1016/j.bbi.2017.02.008
Muthuswamy, Ravikumar ; Okada, Nana J. ; Jenkins, Frank J. ; McGuire, Kandace ; McAuliffe, Priscilla F. ; Zeh, Herbert J. ; Bartlett, David L. ; Wallace, Callen ; Watkins, Simon ; Henning, Jill D. ; Bovbjerg, Dana H. ; Kalinski, Pawel. / Epinephrine promotes COX-2-dependent immune suppression in myeloid cells and cancer tissues. In: Brain, Behavior, and Immunity. 2017 ; Vol. 62. pp. 78-86.
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AU - McAuliffe, Priscilla F.

AU - Zeh, Herbert J.

AU - Bartlett, David L.

AU - Wallace, Callen

AU - Watkins, Simon

AU - Henning, Jill D.

AU - Bovbjerg, Dana H.

AU - Kalinski, Pawel

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