Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.26.9 (ribonuclease)
 6,589 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chemokines play a major role in the recruitment of inflammatory cells during acute lung injury. Adult and newborn C57BL/6 mice were exposed to > 95% oxygen for up to 72 hours and 7 days, respectively. Chemokine mRNA abundance was evaluated in whole lung RNA by ribonuclease protection assay and in tissue sections by in situ hybridization. Monocyte chemoattractant protein (MCP)-1, macrophage inflammatory protein (MIP)-2, and interferon gamma-induced protein (IP)-10 mRNAs were present in whole newborn lung by 4 days of hyperoxia and were markedly elevated by 7 days. Levels of mRNA for MCP-1, MIP-1 alpha, and MIP-2 were elevated to a lesser extent by 72 hours of hyperoxia in adults. MCP-1 mRNA abundance was moderately elevated in scattered areas of perivascular tissue, peribronchiolar tissue, and the alveolar interstitium in 4-day hyperoxic newborns and markedly upregulated diffusely throughout the peripheral airspaces in 7-day hyperoxic newborns. MCP-1 mRNA abundance was limited to scattered perivascular areas and airspaces in 72-hour hyperoxic adults. These differences in the intensity, timing, and distribution of chemokine mRNA abundance between adult and newborn mice may help to explain the marked differences in their susceptibility to oxygen injury.
 ...
PMID:Chemokine mRNA alterations in newborn and adult mouse lung during acute hyperoxia. 977 77

Keloids are characterized by a net accumulation of collagen. To date, the role of growth factors and various cytokines in the pathogenesis of these lesions has not been fully characterized. Interleukin-6 (IL-6) is an important immunoregulatory cytokine that has been implicated in a number of fibrotic autoimmune diseases such as scleroderma, interstitial nephritis, and pulmonary interstitial fibrosis. However, the role of IL-6 in the development of keloids has yet to be defined. This study demonstrates increased expression of the IL-6 gene in fibroblasts isolated from patients with keloids when compared with control fibroblasts using the ribonuclease protection assay. Subsequent detection of increased levels of IL-6 secretion by keloid fibroblasts is also demonstrated under unstimulated and stimulated conditions using serum and interferon gamma (IFN-gamma) (unstimulated: 0.3694 + 0.2499 pg/cell vs 0.0662 + 0.0786 pg/cell, P = 0.0137; serum: 1.066 + 0.513 pg/cell vs 0.233 + 0.231 pg/cell, P = 0.0027; serum and IFN-gamma: 1.286 + 0.395 pg/cell vs 0.244 + 0.199 pg/cell, P < 0.0001). These results suggest that IL-6 may play a significant role in the pathogenesis of keloids.
 ...
PMID:Elevated interleukin-6 expression in keloid fibroblasts. 1072 Apr 55

This study addresses a mechanism by which lymphocytes may promote vascular endothelial growth factor (VEGF) expression and angiogenesis in immune inflammation. Resting human umbilical endothelial cells (HUVECs) were found to express low levels of VEGF messenger RNA (mRNA) by reverse transcription polymerase chain reaction and ribonuclease protection assay with little or no change in expression following activation by cytokines, including tumor necrosis factor-alpha, interleukin (IL)-1, interferon gamma, or IL-4. In contrast, treatment of HUVECs and monocytes with soluble CD40 ligand (sCD40L) resulted in a marked dose-dependent induction of VEGF mRNA (approximately 4-fold), which peaked between 1 and 5 hours post-stimulation. Transient transfection of HUVECs was performed with a luciferase reporter construct under the control of the human VEGF promoter. Treatment of transfected HUVECs with sCD40L was found to enhance luciferase activity (approximately 4-fold) compared with controls, similar to the relative fold induction in mRNA expression in parallel cultures. Thus, CD40-dependent VEGF expression was a result of transcriptional control mechanisms. Treatment of HUVECs with sCD40L was also found to function in vitro to promote growth and proliferation in a VEGF-dependent manner, and CD40-dependent HUVEC growth was comparable to that found following treatment with recombinant human VEGF. Furthermore, subcutaneous injection of sCD40L in severe combined immunodeficient and nude mice induced VEGF expression and marked angiogenesis in vivo. Taken together, these findings are consistent with a function for CD40L-CD40 interactions in VEGF-induced angiogenesis and define a mechanistic link between the immune response and angiogenesis. (Blood. 2000;96:3801-3808)
 ...
PMID:Ligation of CD40 induces the expression of vascular endothelial growth factor by endothelial cells and monocytes and promotes angiogenesis in vivo. 1109 63

Differential modulation has been demonstrated in interleukin-4 (IL-4), IL-10, and interferon gamma (IFN-gamma) mRNA and protein secretion patterns of cells isolated from the draining lymph nodes of mice following exposure to T cell and respiratory sensitizers. Using a multiprobe ribonuclease protection assay, the following investigation examined the mRNA expression patterns of multiple cytokines associated with respiratory sensitization for modulation following exposure to chemicals known primarily to induce irritation (sodium lauryl sulfate), respiratory sensitization (toluene diisocyanate), or T cell-mediated hypersensitivity (dinitrofluorobenzene) responses. On days 0 and +5 female BALB/c mice were exposed to either test article or vehicle on the shaven dorsal lumbar region; on days +10 through +12 the mice received test article on the dorsal aspect of each ear. On day +13 animals were euthanized, draining lymph nodes were excised, and mRNA was isolated immediately or following 24 or 48 h of culture in the presence or absence of concanavalin (Con) A. Differential expression of cytokine mRNA was most notable following 24 h incubation with Con A. Modulation of IL-4, -10, and IFN-gamma following chemical exposure was consistent with previous studies. In addition, IL-9, -13, and -15 were significantly elevated only following toluene diisocyanate exposure. Further investigations of these cytokines may provide additional insight into the mechanisms of chemically induced respiratory sensitization and provide endpoints for the detection of a chemical's ability to elicit IgE-mediated hypersensitivity responses.
 ...
PMID:The determination of draining lymph node cell cytokine mRNA levels in BALB/c mice following dermal sodium lauryl sulfate, dinitrofluorobenzene, and toluene diisocyanate exposure. 1124 17

Fumonisin B(1) (FB(1)), a carcinogenic mycotoxin produced primarily by fungus Fusarium verticillioides in corn, causes several fatal animal diseases. In mice, liver is the primary site of its toxicity. Our previous study showed that maximum induction of interferon gamma (IFNgamma) and tumor necrosis factor alpha (TNFalpha) was observed at 4 and 8 h, respectively, after an acute po FB(1) treatment. To further investigate the time-related induction of other cytokines and genes involved in apoptosis signaling, male BALB/c mice were administered orally with either saline or 25 mg/kg of FB(1) and sampled 4 or 8 h after treatment. Expression of various genes was analyzed by ribonuclease protection assay. FB(1) treatment caused increased expression of TNFalpha and interleukin (IL)-1beta in both liver and kidney, whereas IL-1alpha and IL-1 receptor antagonist (IL-1Ra) expression was induced only in the liver. Expression of TNFalpha signaling molecules, TNF receptor 55 and receptor interacting protein, was increased in liver and kidney after FB(1) treatment. Caspase 8 expression was increased only in liver with no changes in kidney with FB(1). FB(1) treatment induced expression of Fas in liver and kidney with no alterations in Fas signaling molecules, Fas ligand, Fas-associated death domain and Fas-associated protein factor. Treatment of mice with FB(1) increased the expression of B-Myc, c-Myc and Max, oncogenic transcription factors in the kidney. FB(1) toxicity caused induction of cytokine network in liver with involvement of TNFalpha signaling pathway. Increased expression of caspase 8 involved in the TNFalpha signaling pathway may contribute to the apoptosis, whereas IL-1Ra induction could contribute to the proliferating effects observed in FB(1) toxicity.
 ...
PMID:Fumonisin B(1)-induced alterations in cytokine expression and apoptosis signaling genes in mouse liver and kidney after an acute exposure. 1188 48

Prolonged (13 day) topical exposure of BALB/c strain mice to the chemical respiratory allergen trimellitic anhydride (TMA) induces a selective T helper (Th) 2 profile of cytokine secretion in cells isolated from the draining lymph node. The ability of chemical respiratory allergens to elicit preferential type 2 immune responses is a distinguishing characteristic and provides the theoretical basis for cytokine fingerprinting, a novel approach to hazard identification. This study aimed to further characterize the cytokine expression profile induced by TMA, and to investigate the kinetics of cytokine production at both the protein and mRNA level by comparison of acute (3 day) and chronic (13 day) exposure regimes. Acute exposure resulted in the expression of high levels of mRNA for both Th1- and Th2-type cytokines, including interleukins 4, 10, 15 (IL-4, IL-10, IL-15) and interferon gamma (IFN-gamma), and the inflammatory cytokine IL-6, as determined by ribonuclease protection assay (RPA). However, following chronic exposure marked down-regulation of message for IL-6 and IFN-gamma was observed along with concomitant up-regulation of IL-4 and IL-10 expression. These cytokine mRNA profiles were broadly paralleled at the protein level. There was also a marked increase with time of mRNA for the Th2 cytokine IL-9, a cytokine not associated previously with chemical allergy. These data show that as the immune response to TMA develops, the cytokine gene expression profile of allergen-activated lymph node cells evolves from a mixed Th1/Th2 phenotype to a more polarized Th2 profile.
 ...
PMID:Temporal changes in cytokine gene expression profiles induced in mice by trimellitic anhydride. 1242 62