Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.24.59 (MIP)
 4,906 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Macrophage inflammatory protein-1 (MIP-1), a novel cytokine composed of alpha/beta subunits, is released from macrophages during infection. MIP-1 injected intravenously in the rabbit or into the anterior hypothalamic, preoptic area (AH/POA) of the rat causes an intense fever, which is not blocked by prostaglandin synthesis inhibitors, ibuprofin or indomethacin, respectively. The purpose of this study was to determine the role of de novo protein synthesis on the fever evoked by MIP-1 applied to thermosensitive cells of the AH/POA. Guide cannulae were implanted bilaterally above the AH/POA or ventral septal area (VSA) and medially above the third cerebral ventricle in each of 11 male Sprague-Dawley rats. Following postoperative recovery, body temperature (Tb) was monitored by a colonic thermistor probe. The bilateral microinjection of MIP-1 in a dose of 14 pg per 0.5 microliters into the AH/POA caused a biphasic elevation in Tb to 0.9 +/- 0.2 degrees C within 1.0 h, which reached 1.5 +/- 0.2 degrees C within 3.0 h, and persisted for over 6.0 h. An identical injection of MIP-1 into the VSA increased Tb biphasically to 0.1 +/- 0.1 degrees C within 1.0 h and to 0.8 +/- 0.3 degrees C within 3.0 h. The infusion into the third ventricle of 80 micrograms/10 microliters of the inhibitor of protein synthesis, anisomycin, either 10 or 30 min before the microinjection of MIP-1 into the AH/POA, attenuated significantly the rise in Tb for 1.0 to 3.0 h or 2.5 to 3.0 h, respectively. These results coincide with the earlier finding that anisomycin inhibits both endotoxin- and IL-1 beta-induced fevers.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Fever evoked by macrophage inflammatory protein-1 (MIP-1) injected into preoptic or ventral septal area of rats depends on intermediary protein synthesis. 831 99

Mononuclear phagocyte (M phi) recruitment and activation is a hallmark of a number of chronic inflammatory diseases of the lung, including sarcoidosis and idiopathic pulmonary fibrosis (IPF). We hypothesized that macrophage inflammatory protein-1 (MIP-1 alpha), a peptide with leukocyte activating and chemotactic properties, may play an important role in mediating many of the cellular changes that occur in sarcoidosis and IPF. In initial experiments, we demonstrated that human rMIP-1 alpha exerted chemotactic activities toward both polymorphonuclear leukocytes and monocytes, and these activities were inhibited by treatment with rabbit anti-human MIP-1 alpha antiserum. In support of the potential role of MIP-1 alpha in interstitial lung disease, we detected MIP-1 alpha in the bronchoalveolar lavage fluid of 22/23 patients with sarcoidosis (mean 443 +/- 76 pg/ml) and 9/9 patients with IPF (mean 427 +/- 81 pg/ml), whereas detectable MIP-1 alpha was found in only 1/7 healthy subjects (mean 64 +/- 64 pg/ml). In addition, we found a 2.5- and 1.8-fold increase in monocyte chemotactic activity in BALF obtained from patients with sarcoidosis and IPF respectively, as compared to healthy subjects, and this monocyte chemotactic activity, but not neutrophil chemotactic activity, was reduced by approximately 22% when bronchoalveolar lavage fluid from sarcoidosis and IPF patients were preincubated with rabbit antihuman MIP-1 alpha antibodies. To determine the cellular source(s) of MIP-1 alpha within the lung, we performed immunohistochemical analysis of bronchoalveolar lavage cell pellets, transbronchial biopsies, and open lung biopsies obtained from patients with IPF and sarcoidosis. Substantial expression of cell-associated MIP-1 alpha was detected in M phi, including both alveolar AM phi and interstitial M phi. In addition, interstitial fibroblasts within biopsies obtained from sarcoid and IPF patients also expressed immunoreactive MIP-1 alpha. Minimal to no detectable MIP-1 alpha was expressed in alveolar M phi from healthy subjects or interstitial cells in lung biopsy specimens obtained from patients undergoing thoracotomy for malignancy. Furthermore, pulmonary fibroblasts isolated from patients with IPF produced greater amounts of MIP-1 alpha after challenge with IL-1 beta than did similarly treated pulmonary fibroblasts recovered from patients without fibrotic lung disease. Our findings suggest that MIP-1 alpha is expressed in increased amounts within the airspace and interstitium of patients with sarcoidosis and IPF, and that this cytokine may be an important mediator of both M phi activation and recruitment that characterize these disease states.
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PMID:Macrophage inflammatory protein-1 alpha expression in interstitial lung disease. 836 Apr 96

The cytokines are important components of the brain-immune axis. Recent work has shown that [125I]IL-1 alpha and [125I]IL-1 beta are transported from the blood into the brain by a saturable system. Here we show that murine tumor necrosis factor alpha (mTNF alpha) labeled with 125I (I-mTNF alpha) crosses the blood-brain barrier (BBB) after i.v. injection by a transport system different from that for the interleukins. Self inhibition with mTNF alpha showed that this transport system was saturable, and lack of inhibition by IL-1 alpha, IL-1 beta, IL-6, or MIP-1 alpha showed selectivity of the system. High performance liquid chromatography (HPLC) of the radioactivity recovered from brain and from cerebrospinal fluid after the i.v. injection of I-mTNF alpha showed that the cytokine crossed the BBB largely in intact form. Capillary depletion showed that the accumulation of I-mTNF alpha in the cerebral cortex was due to passage across the BBB rather than to sequestration by capillaries. Transport rate was not changed by acute treatment with the neurotoxin aluminium or by acute and chronic treatment with the cationic chelator deferoxamine, but it was more than three times faster in neonatal rats. Efflux of I-mTNF alpha from the brain was slower than would have been predicted based on reabsorption of cerebrospinal fluid, suggesting that TNF alpha is sequestered by the brain. The BBB was not disrupted by up to 50 micrograms kg-1 of mTNF alpha i.v. in either adult mice or neonatal rats as assessed by the BBB's impermeability to radioactively labeled albumin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Murine tumor necrosis factor alpha is transported from blood to brain in the mouse. 837 Jul 68

Langerhans cells (LC) are Ag-presenting cells required for induction of primary immune responses in skin. After activation by Ag, LC express increased levels of MHC class II Ag, exhibit increased accessory cell activity, and migrate to regional lymph nodes where they stimulate T cells. One of the earliest manifestations of LC activation is the accumulation of increased amounts of IL-1 beta mRNA in LC within 15 min after exposure to contact allergens in vivo. To determine if enhanced IL-1 beta production by LC could be causally linked to epicutaneous sensitization, we injected IL-1 beta intradermally into the ears of BALB/c mice and extracted total epidermal RNA 4 h later. A quantitative reverse transcriptase-polymerase chain reaction technique was used to compare changes in IL-1 alpha, IL-1 beta, macrophage inflammatory protein 2, IL-10, TNF-alpha, and 1-A alpha chain mRNA signals caused by intradermally-injected IL-1 beta to those caused by intradermal IL-1 alpha or TNF alpha, or by topical application of the contact allergen trinitrochlorobenzene (3% TNCB). Intradermal injection of 25 ng IL-1 beta resulted in 5-to 100-fold enhancement of mRNA signals for IL-1 alpha, IL-1 beta, MIP-2, IL-10, TNF alpha, and class II I-A alpha, mimicking the changes caused by allergen. In contrast, injection of equivalent amounts of IL-1 alpha or TNF alpha did not significantly alter the epidermal cytokine pattern. Simulating the effects of topically applied TNCB, intradermally-injected IL-1 beta (but not IL-1 alpha or TNF alpha) also caused enhancement of LC MHC class II expression. In addition, LC derived from IL-1 beta-injected skin were 2 to 3 times more potent accessory cells in an anti-CD3 proliferation assay than LC from IL-1 alpha or sham-injected skin. Finally, injection of hamster anti-mIL-1 beta mAb into the skin prior to TNCB treatment completely prevented sensitization to this allergen, although injections of similar amounts of hamster anti-mIL-1 alpha mAb or PBS were without effect. Taken together, our data indicate that dendritic cell-derived IL-1 beta may be a critical molecule required for initiation of primary immune responses in skin.
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PMID:An essential role for Langerhans cell-derived IL-1 beta in the initiation of primary immune responses in skin. 847 27

We present a detailed analysis of cytokine expression patterns of the two permanent human bone marrow stromal cell lines, L87/4 and L88/5. These cell lines, previously established in our laboratory, are highly radiotolerant without cell detachment and support long-term cultures of CD(34+)-enriched human cord blood cells. RT-PCR analysis of 22 different cytokines or cytokine receptor mRNAs showed an almost identical expression pattern in the two stromal cell lines compared to primary human Dexter-type stroma. Since stromal feeder lines employed in long-term cultures usually are irradiated and grown in media containing corticosteroids, we analyzed the impact of irradiation and dexamethasone on cytokine production in the two cell lines by RT-PCR, Northern blot analysis, bioassays, and RIAs. By RT-PCR analysis, constitutive mRNA expression of c-kit, G-CSF, GM-CSF, IL-1 beta, IL-6, IL-7, IL-8, IL-11, Kit ligand (KL), LIF, M-CSF, MIP-1 alpha, TGF-beta, and TNF-alpha was demonstrated in both cell lines, with L87/4 a more potent cytokine producer than L88/5. Northern blot data showed an increase in mRNA levels for GM-CSF, IL-1 beta, and LIF by irradiation and IL-1 alpha treatment in both cell lines. IL-1 alpha-induced GM-CSF, IL-1 beta, IL-6, IL-11, and LIF mRNA levels were reduced by the addition of dexamethasone, whereas dexamethasone had no influence on the amounts of IL-1 alpha-induced G-CSF mRNA. L87/4 and, to a lower extent, L88/5 cells showed dexamethasone-dependent increases in KL mRNA, while KL mRNA levels were not stimulated by IL-1 alpha.
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PMID:Constitutive and modulated cytokine expression in two permanent human bone marrow stromal cell lines. 853 85

Biologically-active molecules secreted from alveolar macrophages, such as cytokines, have been proposed to be involved in the induction of pulmonary toxicity and inflammation in response to the inhalation of oxidant gas pollutants such as NO2 and O3. Despite this, mechanistic studies are hampered by the difficulty in obtaining control macrophages from human subjects, and the intrinsic variability of such primary cells. It is, thus, of importance to develop alternative models for such studies. Here, we have characterised expression kinetics of the mRNAs for tumour necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), macrophage inflammatory protein-1 alpha (MIP-1 alpha) and macrophage inflammatory protein-1 beta (MIP-1 beta) in confluent cultures of the murine IC-21 macrophage line in response to LPS. The secretion of TNF-alpha protein into the medium, assayed by L-929 cell bioassay, closely followed the expression of its mRNA in response to the LPS stimulus. In contrast to LPS, the exposure of IC-21 cells to either air or various concentrations of NO2 in air between 2 and 20 ppm, in an inverted plate exposure model, failed to induce the expression of any of the cytokine mRNAs probed. We conclude that the IC-21 cell line may represent a suitable model for studying the role of stimulated cytokine gene expression in inflammation and that the early events in the pulmonary inflammatory response to the inhalation of NO2 do not involve stimulated release of TNF-alpha, IL-1 beta or MIP-1 alpha/MIP-1 beta from macrophages.
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PMID:Direct exposure to nitrogen dioxide fails to induce the expression of some inflammatory cytokines in an IC-21 murine macrophage cell model. 856 Apr 94

The mRNA expression for 21 kinds of cytokines was measured in six human esophageal cancer cell lines using RT-PCR. More than moderate levels of RNA for IL-1 alpha were expressed in six of six cell lines, IL-1 beta in four, IL-6 in six, IL-7 in five, IL-10 in six, G-CSF in six, GM-CSF in six, SCF in six, MIP-2 beta in two, and LIF in six. None of the tumors expressed detectable message for IL-2, 3, 4, 5, 8, 11, 13, or IRAP after 30 cycles of PCR amplification. IL-1 alpha, IL-6, M-CSF, and GM-CSF levels in the culture supernatants were detectable using ELISA in three of six, four of six, one of six, and six of six ECCs, respectively. IL-1 beta, IL-2, TNF-alpha, and G-CSF were not detectable in all ECCs. There was no correlation between cytokine mRNA expression and production. These results suggest the existence of a complicated cytokine network around esophageal carcinomas that may affect their growth and proliferation.
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PMID:Cytokine mRNA expression patterns in human esophageal cancer cell lines. 859 Mar 2

Once infected by obligate intracellular pathogens, monocytes/macrophages release cytokines that activate natural killer (NK) cells. NK cells in turn produce and secrete monocyte/macrophage activating factors such as interferongamma (IFN-gamma), which are important in the early control of these infections. Here we demonstrate that human NK cells are potent producers of another monocyte/macrophage-activating factor, macrophage inflammatory protein-1 alpha (MIP-1 alpha). Fresh NK cells produce negligible amounts of MIP-1 alpha after stimulation with the monocyte-derived cytokines IL-12, TNF-alpha, IL-1 beta, or IL-10, while stimulation with IL-15 alone results in modest MIP-1 alpha production. Abundant NK cell production MIP-1 alpha is seen after costimulation with IL-12 and IL-15, and is dose-dependent. Combinations of IL-12, with TNF-alpha, IL-1 beta, or IL-10 are substantially less effective inducers of MIP-1 alpha production by NK cells. NK cell MIP-1 alpha mRNA transcripts were detectable within 1 h after costimulation with IL-12 plus IL-15 and steadily increased over 24 h, with a concomitant increase in protein production detectable at 12 h. Resting NK cells constitutively express mRNA transcript for a MIP-1 alpha receptor, and costimulation with IL-12 and IL-15 upregulates its level of expression. Equilibrium binding studies with radioiodinated MIP-1 alpha were consistent with the induction of a single class of high affinity MIP-1 alpha receptors on NK cells costimulated with IL-12 and IL-15. Addition of exogenous MIP-1 alpha to resting NK cells did not enhance cytokine production, but did increase NK cytotoxic activity. The requirement for IL-15 as a critical cofactor for NK cell production MIP-1 alpha suggests a potentially unique role for this monocyte-derived cytokine in combination with IL-12. As MIP-1 alpha is known to potentiate the action of IFN-gamma on monocytes and to suppress human immunodeficiency virus replication, the NK cell's production of MIP-1 alpha may be important during the innate immune response to infection.
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PMID:Human natural killer cells produce abundant macrophage inflammatory protein-1 alpha in response to monocyte-derived cytokines. 867 82

Several studies have shown that CC chemokines attract T lymphocytes, and that CD45RO+, memory phenotype cells are considered to be the main responders. The results, however, have often been contradictory and the role of lymphocyte activation and proliferation has remained unclear. Using CD45RO+ blood lymphocytes cultured under different stimulatory conditions, we have now studied chemotaxis as well as chemokine receptor expression. Expression of the RANTES/MIP-1 alpha receptor (CC-CKR1) and the MCP-1 receptor (CC-CKR2) was highly correlated with migration toward RANTES, MCP-1, and other CC chemokines, and was strictly dependent on the presence of IL-2 in the culture medium. Migration and receptor expression were rapidly downregulated when IL-2 was withdrawn, but were fully restored when IL-2 was added again. The effect of IL-2 could be partially mimicked by IL-4, IL-10, or IL-12, but not by IL-13, IFN gamma, IL-1 beta, TNF-alpha, or by exposure to anti-CD3, anti-CD28 or phytohemagglutinin. Activation of fully responsive lymphocytes through the TCR/CD3 complex and CD28 antigen actually had the opposite effect. It rapidly downregulated receptor expression and consequent migration even in the presence of IL-2. In contrast to the effects on CC chemokine receptors, stimulation of CD45RO+ T lymphocytes with IL-2 neither induced the expression of the CXC chemokine receptors, IL8-R1 and IL8-R2, nor chemotaxis to IL-8. The prominent role of IL-2 in CC chemokine responsiveness of lymphocytes suggests that IL-2-mediated expansion is a prerequisite for the recruitment of antigen-activated T cells into sites of immune and inflammatory reactions.
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PMID:Interleukin-2 regulates CC chemokine receptor expression and chemotactic responsiveness in T lymphocytes. 876 Jul 84

The purpose of this study was to investigate the role of pyrogenic cytokines, such as IL-1 beta, IL-6 and MIP-1 beta, in the mechanisms underlying the hyperthermic response of rats to central injection of PGE2. Thus, specific murine neutralizing antibodies against these cytokines were micro-injected directly into the anterior hypothalamic, preoptic area (AH/POA) of unrestrained rats just before intracerebroventricular injection of PGE2. The significant hyperthermia induced by PGE2 was markedly suppressed by micro-injection of anti-IL-6 and partially attenuated by anti-IL-1 beta. However, the micro-injection of anti-MIP-1 beta failed to alter the hyperthermic response. The results indicate that PGE2-induced hyperthermia is presumably mediated through actions of IL-6 on the thermosensitive cells of the AH/POA and confirm that distinct and alternate pathways exist in the rat brain for the induction of fever.
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PMID:Role of interleukin-1 beta, interleukin-6 and macrophage inflammatory protein-1 beta in prostaglandin-E2-induced hyperthermia in rats. 880 17


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