Blood-Borne Revitalization of the Aged Brain. Castellano JM et al. (2015) In the modern medical era, more diverse and effective treatment options have translated to increased life expectancy. With this increased life span comes increased age-associated disease and the dire need to understand underlying causes so that therapies can be designed to mitigate the burden to health and the economy. Aging exacts a seemingly inevitable multisystem deterioration of function that acts as a risk factor for a variety of age-related disorders, including those that devastate organs of limited regenerative potential, such as the brain. Rather than studying the brain and mechanisms that govern its aging in isolation from other organ systems, an emerging approach is to understand the relatively unappreciated communication that exists between the brain and systemic environment. Revisiting classical methods of experimental physiology in animal models has uncovered surprising regenerative activity in young blood with translational implications for the aging liver, muscle, brain, and other organs. Soluble factors present in young or aged blood are sufficient to improve or impair cognitive function, respectively, suggesting an aging continuum of brain-relevant systemic factors. The age-associated plasma chemokine CCL11 has been shown to impair young brain function while GDF11 has been reported to increase the generation of neurons in aged mice. However, the identities of specific factors mediating memory-enhancing effects of young blood and their mechanisms of action are enigmatic. Here we review brain rejuvenation studies in the broader context of systemic rejuvenation research. We discuss putative mechanisms for blood-borne brain rejuvenation and suggest promising avenues for future research and development of therapies.//////////////////
NCBI Summary:
This antimicrobial gene is one of several chemokine genes clustered on the q-arm of chromosome 17. Chemokines form a superfamily of secreted proteins involved in immunoregulatory and inflammatory processes. The superfamily is divided into four subfamilies based on the arrangement of the N-terminal cysteine residues of the mature peptide. This chemokine, a member of the CC subfamily, displays chemotactic activity for eosinophils, but not mononuclear cells or neutrophils. This eosinophil-specific chemokine is thought to be involved in eosinophilic inflammatory diseases such as atopic dermatitis, allergic rhinitis, asthma and parasitic infections. [provided by RefSeq, Sep 2014]
General function
Ligand
Comment
Cellular localization
Secreted
Comment
Ovarian function
Comment
Bovine eotaxin (CCL11)-an unusual member of the eotaxin group-attracts eosinophils in vitro but is not responsible for eosinophilia in the ovary.
Vogel B,et al .
Under physiological conditions normally characterised by low tissue infiltration of eosinophils, a conspicuous number of these cells are attracted into the human and ruminant ovary. Eosinophils suddenly increase in the thecal layer of the preovulatory follicle and corpus luteum at very early development. Currently, we only have a limited understanding of the mechanism for the recruitment of the ovarian eosinophils. Eotaxin (CCL11) may be one of the chemoattractants involved in stimulating eosinophils to migrate selectively into ovary. As a prerequisite for the analysis of eotaxin expression in the bovine ovary, we determined the complete bovine eotaxin mRNA sequence since it was not available from databases. The bovine eotaxin is the first member of the monocyte chemoattractant protein (MCP)/eotaxin subfamily with two mRNA isoforms varying in length in the untranslated 3'-untranslated region. The unusual amino-acid sequence of bovine eotaxin contains structural features that are so far known to be characteristic for MCP, but not eotaxin. In our microchemotaxis assays, recombinant bovine eotaxin showed a functional pattern orthologous to known eotaxins. Thus, the chimeric structure of bovine eotaxin did not affect the favoured chemotactic activity on eosinophils. Semiquantitative RT-PCR was used to investigate the expression of eotaxin in different regions of the bovine ovary. We only detected faint eotaxin mRNA signals that did not indicate physiological significance even in stimulated granulosa cell cultures, follicle-derived macrophages or fibroblasts. Taken together, bovine eotaxin attracts eosinophils in vitro but is not responsible for eosinophilia in the ovary. Its unusual chimeric structure confirms the unity of the MCP/eotaxin subfamily of CC chemokines and distinguishes it from other CC chemokine subfamilies.
Expression regulated by
LH
Comment
Rapid and Transient Upregulation of CCL11 (Eotaxin-1) in Mouse Ovary During Terminal Stages of Follicular Development. Kuwabara Y et al. PROBLEM: This study aimed to investigate the regulation of expression, localization and physiological role of the CCL11/CCR3 axis in mouse ovary during the periovulatory period. METHOD OF STUDY: CCL11/CCR3 expression in the mouse ovary after treatment with pregnant mare serum gonadotropin (PMSG) followed by human chorionic gonadotropin (hCG) 48hr later was assessed in vivo and in 3-dimensional cultures in vitro. RESULTS: Real-time RT-PCR analyses revealed transient CCL11 mRNA upregulation 6hr after hCG treatment. Immunohistochemical staining of serial ovarian sections demonstrated overlapping expression of CCL11, CCR3 and CD31 endothelial cell marker in the theca-interstitial layer at 10hr after hCG treatment. In vitro 3-dimensional cultures of periovulatory ovarian tissues demonstrated that treatment with anti-CCL11 neutralizing antibody significantly decreased CD31 transcript. CONCLUSIONS: Gonadotropin surge leads to transient CCL11/CCR3 axis upregulation in the ovarian theca-interstitial layer, suggesting that it is involved in periovulatory physiological processes by affecting follicular vessels.
Ovarian localization
Theca, Luteal cells
Comment
Gene expression profiles in the bovine corpus luteum (CL) during the estrous cycle and pregnancy: possible roles of chemokines in regulating CL function during pregnancy. Sakumoto R et al. (2015) To determine functional differences between the corpus luteum (CL) of the estrous cycle and pregnancy in cows, gene expression profiles were compared using a 15 K bovine oligo DNA microarray. In the pregnant CL at days 20-25, 40-45 and 150-160, the expressions of 138, 265 and 455 genes differed by a factor of > 2-fold (P < 0.05) from their expressions in the cyclic CL (days 10-12 of the estrous cycle). Messenger RNA expressions of chemokines (eotaxin, lymphotactin and ENA-78) and their receptors (CCR3, XCR1 and CXCR2) were validated by quantitative real-time PCR. Transcripts of eotaxin were more abundant in the CL at days 40-45 and 150-160 of pregnancy than in the cyclic CL (P < 0.01). In contrast, the mRNA expressions of lymphotactin, ENA-78 and XCR1 were lower in the CL of pregnancy (P < 0.05). Messenger RNAs of CCR3 and CXCR2 were similarly detected both in the cyclic and pregnant CL. Tissue protein levels of eotaxin were significantly higher in the CL at days 150-160 of pregnancy than in the CL at other stages, whereas the lymphotactin protein levels in the CL at days 20-25 of pregnancy were lower (P < 0.05). Immunohistochemical staining showed that CCR3 was expressed in the luteal cells and that XCR1 was expressed in both the luteal cells and endothelial cells. Collectively, the different gene expression profiles may contribute to functional differences between the cyclic and pregnant CL, and chemokines including eotaxin and lymphotactin may regulate CL function during pregnancy in cows.//////////////////