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Macrophage inflammatory protein (MIP)1α and MIP1β differentially regulate release of inflammatory cytokines and generation of tumoricidal monocytes in malignancy

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Abstract

The C–C chemokines, macrophage inflammatory protein (MIP)1α and MIP1β are potent chemoattractants for the monocytes, which form an important component of the stroma of tumor tissue and may regulate tumor growth and associated inflammation. We examined the role of MIP1α and MIP1β in inducing the release of inflammatory cytokines and the generation of tumoricidal monocytes from the peripheral blood monocytes (PBM) of healthy women and patients with carcinoma of breast (CaBr). Interleukin-1 (IL-1) and tumor necrosis factor (TNF) α release by the PBM was markedly stimulated by MIP1α in CaBr patients, but only marginally so in healthy women. In contrast, MIP1β stimulated the release of these cytokines by the PBM of healthy women, but failed to do so in CaBr patients. MIP1α, but not MIP1β, synergized with LPS in inducing the release of IL-1 from the PBM of both healthy women and CaBr patients. Both MIP1α and MIP1β augmented respiratory bursts in PBM and generated tumoricidal PBM that killed T24 cells, MIP1α being more effective in CaBr patients and MIP1β in healthy women. IFN-γ co-stimulated and IL-4 suppressed MIP1α and β-induced cytotoxicity in PBM. The synergy of IFN-γ was more marked with MIP1α than with MIP1β. The differential effects of MIP1α and MIP1β on the PBM of healthy women and CaBr patients co-related with the levels of expression of CCR1 and CCR5 in these monocytes. The expression of CCR5 was higher than that of CCR1 in the PBM of healthy women and the PBM of the CaBr patients showed overexpression of CCR1 and downregulation of CCR5.

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Acknowledgements

The authors wish to thank Dr. Ji Ming Wang for reviewing the work, Dr. Ratna Biswas for editorial assistance, and Mr. Sumit Kr. Majumder for secretarial help.

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Authors and Affiliations

  1. Department of Bioengineering, University of Pittsburgh, 260 Kappa Drive, Suite 106, Pittsburgh, PA, 15238, USA

    Nawal K. Sharma

  2. Division of Infectious Diseases, School of Medicine, Scaife Hall, University of Pittsburgh, 3550 Terrace Street, Pittsburgh, PA, 15261, USA

    Anamika Nath

  3. Department of Immunoregulation and Immunodiagnostics, Chittaranjan National Cancer Institute, 700026, Kolkata, India

    Sreya Chattopadhya & Utpala Chattopadhyay

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  1. Anamika Nath
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Correspondence to Nawal K. Sharma.

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Nath, A., Chattopadhya, S., Chattopadhyay, U. et al. Macrophage inflammatory protein (MIP)1α and MIP1β differentially regulate release of inflammatory cytokines and generation of tumoricidal monocytes in malignancy. Cancer Immunol Immunother 55, 1534–1541 (2006). https://doi.org/10.1007/s00262-006-0149-3

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