Title |
The human breast cancer-associated protein, the prolactin-inducible protein (PIP), regulates intracellular signaling events and cytokine production by macrophages
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Published in |
Immunologic Research, March 2018
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DOI | 10.1007/s12026-018-8987-6 |
Pubmed ID | |
Authors |
Olivia Ihedioha, Anne A. Blanchard, Jyoti Balhara, Ifeoma Okwor, Ping Jia, Jude Uzonna, Yvonne Myal |
Abstract |
The prolactin-inducible protein (PIP) is considered a valuable biomarker that is associated with both benign and malignant pathological conditions of the mammary gland. The function of PIP in breast tumorigenesis remains unknown; however, evidence from our laboratory and others suggest that it regulates host immunity. Studies with PIP-deficient (PIP-/-) mice demonstrated significantly lower numbers of CD4+T cells in their secondary lymphoid organs, impaired Th1 response, and impaired nitric oxide (NO) production. To further delineate the immunoregulatory role of PIP, we compared the expression of IFN-γR and TLR4, pro-inflammatory cytokine production, and intracellular signaling events by IFN-γ and lipopolysaccharide (LPS)-stimulated macrophages from wild-type (WT) and PIP-/-mice. We showed that although the expressions of IFN-γR and TLR4 were comparable, productions of pro-inflammatory cytokines were decreased in PIP-/-macrophages. This was associated with decreased phosphorylation of mitogen-activated protein kinase (MAPK) and signal transducer of activation of transcription (STAT) proteins in macrophages from PIP-/-mice. Interestingly, the expression of suppressors of cytokine signaling (SOCS) 1 and 3 proteins, known to suppress IFN-γ and LPS signaling, was higher in PIP-/-macrophages compared to those from WT mice. Collectively, our studies show that deficiency of PIP significantly affects intracellular signaling events leading to decreased pro-inflammatory cytokine production, and further confirms a role for PIP as an important immunoregulatory protein. This direct link between PIP and cell-mediated immunity, a key component of the immune system that is critical for cancer control, may have significant therapeutic implications. |
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Unknown | 5 | 38% |