The prolactin receptor is expressed in macrophages within human carotid atherosclerotic plaques: a role for prolactin in atherogenesis?

Abstract

Atherosclerotic vascular disease is the consequence of a chronic inflammatory process, and prolactin has been shown to be a component of the inflammatory response. Additionally, recent studies indicate that prolactin contributes to an atherogenic phenotype. We hypothesized that this may be the result of a direct effect of prolactin on atherogenesis through activation of the prolactin receptor. Human carotid atherosclerotic plaques were obtained from patients by endarteriectomies. The mRNA of prolactin receptor, but not of prolactin, was detected in these atherosclerotic plaques by quantitative realtime PCR. In situ hybridization confirmed the expression of the prolactin receptor in mononuclear cells. Analysis at the protein level using immunohistochemistry and immunoelectron microscopy revealed that the prolactin receptor was abundantly present in macrophages near the lipid core and shoulder regions of the plaques. Our findings demonstrate that the prolactin receptor is present in macrophages of the atherosclerotic plaque at sites of most prominent inflammation. We therefore propose that prolactin receptor signaling contributes to the local inflammatory response within the atherosclerotic plaque and thus to atherogenesis.

Prolactin regulates TRPV1, TRPA1, and TRPM8 in sensory neurons in a sex-dependent manner: Contribution of prolactin receptor to inflammatory pain

“…The function of PRL in the central nervous system could be evaluated by a pharmacological approach using the specific PRL-R antagonist ⌬G129R-hPRL that could be applied locally or in spinal cord to define the specific site of action for the PRL system in inflammatory hyperalgesia. Third, inflammation can regulate PRL-R expression in a variety of cells (24,61). Even though our results show that the short and long forms of PRL-R are not regulated at the transcriptional level in the DRG and spinal cord, membrane density of PRL-R in certain spinal cord cells could still be altered.…”

The prolactin receptor is expressed in rheumatoid arthritis and psoriatic arthritis synovial tissue and contributes to macrophage activation

“…Furthermore, PRL has an effect on the proliferation and differentiation of T cells and alters regulatory T cells to contribute to inflammation [9]. Recently, it has been shown that the PRL receptor (PRLR), which belongs to the family of haematopoietic cytokine receptors, is present in human atherosclerotic plaques at the sites of inflammation, primarily on macrophages [10]. Although the potential functional consequences of PRLR ligation on human macrophages have not been examined, PRL induces production of different cytokines, such as IL-1β, IL-12β, IFN-γ and TNF and chemokines by murine peritoneal macrophages [11, 12].…”

Prolactin receptor antagonism uncouples lipids from atherosclerosis susceptibility

“…Of note, PRLR protein expression has also been detected on macrophages locally within human atherosclerotic lesions (Reuwer et al 2011). Thus, prolactin can also directly modulate the immune function.…”