Редактирование: IL4

Interleukin-4 precursor (IL-4) (B-cell stimulatory factor 1) (BSF-1) (Binetrakin) (Lymphocyte stimulatory factor 1) (Pitrakinra)

==Publications==

{{medline-entry
|title=Deficiency in Protein Tyrosine Phosphatase PTP1B Shortens Lifespan and Leads to Development of Acute Leukemia.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/29122767
|abstract=Protein tyrosine phosphatase PTP1B is a critical regulator of signaling pathways controlling metabolic homeostasis, cell proliferation, and immunity. In this study, we report that global or myeloid-specific deficiency of PTP1B in mice decreases lifespan. We demonstrate that myeloid-specific deficiency of PTP1B is sufficient to promote the development of acute myeloid leukemia. LysM-PTP1B  mice lacking PTP1B in the innate myeloid cell lineage displayed a dysregulation of bone marrow cells with a rapid decline in population at midlife and a concomitant increase in peripheral blood blast cells. This phenotype manifested further with extramedullary tumors, hepatic macrophage infiltration, and metabolic reprogramming, suggesting increased hepatic lipid metabolism prior to overt tumor development. Mechanistic investigations revealed an increase in anti-inflammatory M2 macrophage responses in liver and spleen, as associated with increased expression of arginase I and the cytokines [[IL10]] and [[IL4]]. We also documented [[STAT3]] hypersphosphorylation and signaling along with JAK-dependent upregulation of antiapoptotic proteins Bcl2 and BclXL. Our results establish a tumor suppressor role for PTP1B in the myeloid lineage cells, with evidence that its genetic inactivation in mice is sufficient to drive acute myeloid leukemia.  This study defines a tumor suppressor function for the protein tyrosine phosphatase PTP1B in myeloid lineage cells, with evidence that its genetic inactivation in mice is sufficient to drive acute myeloid leukemia. [i]Cancer Res; 78(1); 75-87. ©2017 AACR[/i].
|mesh-terms=* Animals
* Cytokines
* Female
* Leukemia, Myeloid, Acute
* Liver
* Longevity
* Macrophages
* Male
* Mice, Knockout
* Myeloid Cells
* Protein Tyrosine Phosphatase, Non-Receptor Type 1
* Proto-Oncogene Proteins c-bcl-2
* Pyrazoles
* STAT3 Transcription Factor
* STAT5 Transcription Factor
* Spleen
* bcl-X Protein

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5756472
}}
{{medline-entry
|title=Aging Affects Bone Marrow Macrophage Polarization: Relevance to Bone Healing.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28138512
|abstract=Macrophages are an important component of the inflammatory cascade by initiating and modulating the processes leading to tissue regeneration and bone healing. Depending on the local environment, macrophages can be polarized into M1 (pro-inflammatory) or M2 (anti-inflammatory) phenotypes. In order to assess the effects of aging on macrophage function, bone marrow macrophage polarization using primary bone marrow macrophages (BMMs) from young (8 weeks old) and aged (72 weeks old) wild-type male C57BL/6J mice was analyzed. Fluorescence-activated cell sorting (FACS) analysis (CD11b, iNOS, CD206), qRT-PCR (iNOS, [[TNF]]-α, CD206, Arginase 1), and ELISA ([[TNF]]-α, IL-1ra) were performed to compare the M1 and M2 phenotypic markers in young and aged mouse macrophages. Once M1 and M2 macrophage phenotypes were confirmed, the results showed that [[TNF]]-α mRNA was significantly upregulated in aged M1s after interferon gamma (INF-γ) exposure. Arginase 1 and CD206 mRNA expression were still upregulated with [[IL4]] stimulation in aged macrophages, but to a lesser extend than those from younger animals. [[TNF]]-α secretion was also significantly increased in aged M1s compared to young M1s, following lipopolysaccharide (LPS) exposure. However, the IL-1ra secretion did not increase accordingly in aged mice. The results demonstrate that, compared to younger animals, aging of bone marrow derived macrophages increases the resting levels of oxidative stress, and the ratios of pro- to anti-inflammatory markers. These age-related changes in macrophage polarization may explain in part the attenuated response to adverse stimuli and delay in processes such as fracture healing seen in the elderly. Bone healing is a complex process that involves both biological and mechanical factors. Macrophages are key cells that regulate the events involved in bone healing, especially the initial inflammatory phase. In this biological cascade of events, macrophages present as different functional phenotypes including uncommitted (M0), pro-inflammatory (M1), and anti-inflammatory (M2), a process called macrophage polarization. A clear understanding of the effects of aging on macrophage polarization is critical to modulating adverse events such as fractures, atraumatic bone loss, and tissue regeneration in an aging population.

|keywords=* Aging
* Bone healing
* Bone marrowmacrophage
* Polarization
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5270653
}}
{{medline-entry
|title=[[IL4]]/[[STAT6]] Signaling Activates Neural Stem Cell Proliferation and Neurogenesis upon Amyloid-β42 Aggregation in Adult Zebrafish Brain.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27760324
|abstract=Human brains are prone to neurodegeneration, given that endogenous neural stem/progenitor cells (NSPCs) fail to support neurogenesis. To investigate the molecular programs potentially mediating neurodegeneration-induced NSPC plasticity in regenerating organisms, we generated an Amyloid-β42 (Aβ42)-dependent neurotoxic model in adult zebrafish brain through cerebroventricular microinjection of cell-penetrating Aβ42 derivatives. Aβ42 deposits in neurons and causes phenotypes reminiscent of amyloid pathophysiology: apoptosis, microglial activation, synaptic degeneration, and learning deficits. Aβ42 also induces NSPC proliferation and enhanced neurogenesis. Interleukin-4 ([[IL4]]) is activated primarily in neurons and microglia/macrophages in response to Aβ42 and is sufficient to increase NSPC proliferation and neurogenesis via [[STAT6]] phosphorylation through the [[IL4]] receptor in NSPCs. Our results reveal a crosstalk between neurons and immune cells mediated by [[IL4]]/[[STAT6]] signaling, which induces NSPC plasticity in zebrafish brains.
|mesh-terms=* Aging
* Amyloid beta-Peptides
* Animals
* Brain
* Cell Plasticity
* Cell Proliferation
* Interleukin-4
* Microglia
* Nerve Degeneration
* Neural Stem Cells
* Neurogenesis
* Neurons
* Peptide Fragments
* Phenotype
* Protein Aggregates
* STAT6 Transcription Factor
* Signal Transduction
* Zebrafish
|keywords=* Alzheimer’s disease
* Amyloid-β42
* STAT6
* inflammation
* interlukin-4
* neural stem cell
* neuro-immune crosstalk
* neurodegeneration
* regeneration
* zebrafish
|full-text-url=https://sci-hub.do/10.1016/j.celrep.2016.09.075
}}
{{medline-entry
|title=[[IL10]]-driven [[STAT3]] signalling in senescent macrophages promotes pathological eye angiogenesis.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/26260587
|abstract=Macrophage dysfunction plays a pivotal role during neovascular proliferation in diseases of ageing including cancers, atherosclerosis and blinding eye disease. In the eye, choroidal neovascularization (CNV) causes blindness in patients with age-related macular degeneration (AMD). Here we report that increased [[IL10]], not [[IL4]] or [[IL13]], in senescent eyes activates [[STAT3]] signalling that induces the alternative activation of macrophages and vascular proliferation. Targeted inhibition of both [[IL10]] receptor-mediated signalling and [[STAT3]] activation in macrophages reverses the ageing phenotype. In addition, adoptive transfer of [[STAT3]]-deficient macrophages into eyes of old mice significantly reduces the amount of CNV. Systemic and CD163( ) eye macrophages obtained from AMD patients also demonstrate [[STAT3]] activation. Our studies demonstrate that impaired [[SOCS3]] feedback leads to permissive [[IL10]]/[[STAT3]] signalling that promotes alternative macrophage activation and pathological neovascularization. These findings have significant implications for our understanding of the pathobiology of age-associated diseases and may guide targeted immunotherapy. 
|mesh-terms=* Aged
* Aged, 80 and over
* Aging
* Animals
* Eye
* Female
* Humans
* Interleukin-10
* Macrophages
* Macular Degeneration
* Male
* Mice
* Mice, Inbred C57BL
* Middle Aged
* Neovascularization, Pathologic
* Porphyrins
* RAW 264.7 Cells
* Receptors, Interleukin-10
* STAT3 Transcription Factor
* Suppressor of Cytokine Signaling 3 Protein
* Suppressor of Cytokine Signaling Proteins

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4918330
}}
{{medline-entry
|title=LIPID PROFILE AND CYTOKINES INTERACTIONS DURING SUCCESSFUL AGING.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/26087730
|abstract=Aging is accompanied by a loss of homeostasis, which leads to increase of susceptibility and vulnerability to cancers, cardiovascular, neurodegenerative and autoimmune diseases. Numerous studies have been suggested that even in the absence of acute infection ageing associated with chronic low-grade inflammation and the underlying cause of this process may be an immunosenescence as well as shifts production of cytokines levels. However, the results on age-related alterations of these cytokine levels are inconsistent. The main aim of our study was to evaluate how the pro- and anti-inflammatory cytokines and lipoproteins fraction varies through aging as well as how these changes related each other in an apparently healthy population. For this purposes, 220 healthy volunteers were selected on the basis of clinical records and laboratory examinations. Individuals with various health problems were excluded. Fasting triglycerids ([[TG]]), low and high density lipoproteins (LDL and HDL) and cytokines (IL-6, [[IL4]], 10, 17, IFN, [[TNF]]) levels were measured using commercial assay kits. The statistical analysis was performed using SPSS (Chicago, IL, USA). The results revealed that all studied cytokines levels did not fluctuate by gender. LDL means value differ significantly between men and women. Age are not main predictor for HDL, [[TG]], [[IL4]], [[IL6]], IFN circulating levels, however, the production of LDL, IL17 and [[IL10]] showed significant deviations through aging: especially, LDL and IL17 were augmented, while IL-10 were reduced. It is interestingly, that besides the age, LDL levels were correlated with [[TNF]]-alfa and [[IL10]], while triglyceride were only associated with [[IL10]] levels. It has to be note that the correlations did not changes after adjustment of age. The result of our study shown that lipoproteins (LDL, [[TG]]) and cytokines ([[TNF]], [[IL10]], IL17) levels are linked and can be used as a prognostic markers of cardiovascular diseases development. 
|mesh-terms=* Adult
* Aged
* Aged, 80 and over
* Aging
* Cholesterol
* Dyslipidemias
* Female
* Healthy Volunteers
* Humans
* Inflammation
* Lipids
* Lipoproteins
* Male
* Middle Aged
* Triglycerides


}}
{{medline-entry
|title=Ageing related periostin expression increase from cardiac fibroblasts promotes cardiomyocytes senescent.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/25173938
|abstract=Periostin, as an extracellular matrix (ECM) protein, plays a critical role in myocardial fibrosis and also might be involved in the heart inflammatory process since it is a downstream molecule of [[IL4]] and IL13. Considering the possible important role of periostin in heart aging, this study explored periostin expression pattern in both rat and human, the effect of periostin expression on cardiomyocyte senescent and expression of three cytokines (IL13, [[IL4]] and IL6) in different age groups of human. This study found heart aging is associated with increased expression of periostin from cardiac fibroblasts and serum inflammatory cytokines (IL13 and IL6). Excessive periostin expression contributed to cardiomyocyte senescent, which could be alleviated through blocking the Ang-II-TGF β1-MAPK/ERK pathway. Thus, periostin might play an important role in a vicious circle (aging-fibrosis-inflammation-aging) of heart through promoting myocardial fibrosis and cardiomyocyte senescent simultaneously. It is a potential aging marker that could be directly measured in serum. 
|mesh-terms=* Aging
* Angiotensin II
* Animals
* Biomarkers
* Cell Adhesion Molecules
* Cellular Senescence
* Fibroblasts
* Fibrosis
* Gene Expression Regulation
* Humans
* Interleukin-13
* Interleukin-4
* Interleukin-6
* Mitogen-Activated Protein Kinase Kinases
* Myocardium
* Myocytes, Cardiac
* Primary Cell Culture
* Rats
* Rats, Sprague-Dawley
* Signal Transduction
* Transforming Growth Factor beta1
|keywords=* Heart aging
* Inflammation
* Periostin
* Senescent
* TGF-β1
|full-text-url=https://sci-hub.do/10.1016/j.bbrc.2014.08.109
}}