Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0032285 (pneumonia)
 54,520 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The herb, Chrysanthemum zawadskii var, latilobum commomly known as Gu-Jul-Cho in Korea, used in traditional medicine to treat pneumonia, bronchitis, cough, common cold, pharyngitis, bladder-related disorders, gastroenteric disorders, and hypertension. Linarin is the main active compound and the biological mechanisms of its activity are unclear. It is believed that effects of this herb may be exerted through the pluripotent effectors of linarin due to its ability to treat a variety of afflictions. In this study, the effects of linarin on the mouse macrophages cell line, RAW 264.7, were investigated. It was found that linarin could activate macrophages by producing cytokines. Monocytes and tissue macrophages produce at least two groups of protein mediators of inflammation, interleukin 1 (IL-1) and the tumor necrosis factor (TNF). Recent studies have shown that TNF and IL-1 modulate the inflammatory function of endothelial cells, leukocytes, and fibroblasts. TNF-alpha production by macrophages treated with linarin occured in a dose dependent manner. However, IL-1 production was largely unaffected by this natural product. This study demonstrated the ability of linarin to activate macrophages both directly and indirectly. Linarin also affect both cytokine production and nitric oxide inhibition, in addition to the expression of some surface molecules. Nitric oxide (NO), derived from L-argin-ine, is produced by two forms(constitutive and inducible) of nitric oxide synthase (NOS). The NO produced in large amounts by inducible NOS is known to be responsible for the vasodilation and hypotension observed in septic shock. Linarin was found to inhibit NO production in the LPS-activated RAW 264.7 cells. Linarin may be a useful candidate as a new drug for treating endotoxemia and the inflammation accompanied by NO overproduction. The linarin-treated total lymphocytes exhibited cytotoxicity in a dose dependent manner between 20 microg/ml and 40 microg/ml. These results suggest that linarin may function through macrophage activation.
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PMID:The effect of linarin on LPS-induced cytokine production and nitric oxide inhibition in murine macrophages cell line RAW264.7. 1200 31

Prostaglandins (PG) are potent mediators of intercellular communication, and PGE2 at high concentration is immunosuppressive for T-cell-mediated immunity. We studied the kinetics of PGE2 production and the expression of the enzymes related to its synthesis during the course of experimental pulmonary tuberculosis. Secondly, we analysed the pathological and immunological changes produced by the pharmacological suppression of PG production. In BALB/c mice infected via the trachea with Mycobacterium tuberculosis H37Rv there is an initial phase of partial resistance, dominated by type 1 cytokines plus tumour necrosis factor-alpha (TNF-alpha) and expression of the inducible form of nitric oxide synthase (iNOS), followed by a phase of progressive disease. During the early phase of the infection some activated macrophages located in the alveolar-capillary interstitium and in granulomas showed strong PGE2 immunostaining. However, PGE2 concentrations were relatively low and stable. Animals in this early phase of infection were treated with niflumic acid, a potent and specific blocker of cyclo-oxygenase 2, the rate-limiting enzyme of PG production. In comparison with control animals, the suppression of PG synthesis produced higher inflammation and expression of TNF-alpha, interleukin-1alpha and interferon-gamma (IFN-gamma), but almost complete disappearance of iNOS expression, which coexisted with a significant increment of bacterial load. The late progressive phase in this experimental model is characterized by progressive pneumonia, small granulomas and diminished expression of IFN-gamma, TNF-alpha and iNOS in coexistence with high expression of IL-4. Strong PGE2 immunostaining was seen in foamy macrophages localized in the pneumonic areas, and the PGE2 concentration was four-fold higher in this late phase of infection than during the early phase. When PG production was suppressed in animals suffering advanced phase infection, a significant reduction of pneumonia and bacillus load with striking increment of granuloma size was seen, and the expression of IFN-gamma, TNF-alpha and iNOS was also improved. These findings demonstrate a significant participation of PGE2 in the pathogenesis of pulmonary tuberculosis, showing that during the early phase of the infection there are low PGE2 concentrations which contribute to iNOS expression permitting the temporal control of bacillus growth, while the high PGE2 concentrations during the late phase of the disease contribute to down-regulate cell-mediated immunity, permitting disease progression.
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PMID:The role of prostaglandin E2 in the immunopathogenesis of experimental pulmonary tuberculosis. 1204 55

Chlamydia are intracellular bacteria which infect many vertebrates, including humans. They cause a myriad of severe diseases, ranging from asymptomatic infection to pneumonia, blindness or infertility. IFN-gamma plays an important role in defense against acute infection and in the establishment of persistence. Chlamydia have evolved mechanisms to escape IFN-gamma functions. IFN-gamma-mediated effector mechanisms may involve effects on the metabolism of tryptophan or iron, on the inducible NO synthase (iNOS), on the secretion of chemokines and adhesion molecules or on the regulation of T-cell activities. IFN-gamma is secreted by the innate and the adaptive arms of the immune system. Within the former, Chlamydia-infected macrophages express IFN-gamma that in turn mediates resistance to infection. IFN-alpha/beta are pivotal for both IFN-gamma- and iNOS-mediated resistance to chlamydial infection in macrophages.
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PMID:The role of IFN-gamma in the outcome of chlamydial infection. 1208 78

The influence of LPS preincubation on hydrogen peroxide (H(2)O(2))-induced loss of epithelial barrier function was investigated in rat alveolar epithelial type II cells (ATII). Both apical and basolateral H(2)O(2) administration caused a manyfold increase in transepithelial [(3)H]mannitol passage. Apical but not basolateral preincubation of ATII with LPS did not influence control barrier properties but fully abrogated the H(2)O(2)-induced leakage response. The effect of apical LPS was CD14 dependent and was accompanied by a strong up-regulation of NO synthase II mRNA and protein and NO release. Inhibition of NO by N(G)-monomethyl-L-arginine suppressed the LPS effect, whereas it was reproduced by exogenous application of gaseous NO or NO donor agents. Manipulation of the glutathione homeostasis (buthionine-(S,R)-sulfoximine) and the cGMP pathway (1H-(1,2,4)oxadiazolo[4,3-alpha]quinoxaline-1-one; zaprinast) did not interfere with the protective effect of LPS. Superoxide (O*(-)(2)) generation by ATII cells was reduced by exogenous NO and LPS preincubation. O*(-)(2) scavenging with exogenous superoxide dismutase, the intracellular superoxide dismutase analog Mn(III)tetrakis(4-benzoic acid) porphyrin, and the superoxide scavenger nitroblue tetrazolium and, in particular, hydroxyl radical scavenging with hydroxyl radical scavenger 1,3-dimethyl-thiourea inhibited the H(2)O(2)-induced epithelial leakage response. In conclusion, apical but not basolateral LPS preincubation of ATII cells provides strong protection against H(2)O(2)-induced transepithelial leakage, attributable to an up-regulation of epithelial NO synthesis. It is suggested that the LPS-induced NO formation is effective via interaction with reactive oxygen species, including superoxide and hydroxyl radicals. The polarized epithelial response to LPS may be part of the lung innate immune system, activated by inhaled endotoxin or under conditions of pneumonia.
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PMID:Apical, but not basolateral, endotoxin preincubation protects alveolar epithelial cells against hydrogen peroxide-induced loss of barrier function: the role of nitric oxide synthesis. 1213 74

Nitric oxide (NO) has been shown to play a major role in acute lung injury (ALI) after smoke inhalation. In the present study, we developed an ovine sepsis model, created by exposing sheep to smoke inhalation followed by instillation of bacteria into the airway, that mimics human sepsis and pneumonia. We hypothesized that the inhibition of neuronal NO synthase (nNOS) might be beneficial in treating ALI associated with this model. Female sheep (n = 26) were surgically prepared for the study and given a tracheostomy. This was followed by insufflation of 48 breaths of cotton smoke (40 degrees C) into the airway of each animal and subsequent instillation of live Pseudomonas aeruginosa [5 x 10(11) colony forming units (CFU)] into each sheep's lung. All sheep were mechanically ventilated using 100% O2. Continuous infusion of 7-nitroindazole (7-NI), an nNOS inhibitor, NG-monomethyl-l-arginine (l-NMMA), a nonspecific NOS inhibitor, or aminoguanidine (AG), an inducible NOS inhibitor, was started 1 h after insult. The administration of 7-NI improved pulmonary gas exchange (PaO2/FiO2; where PaO2 is arterial PO2 and FiO2 is fractional inspired oxygen concentration) and pulmonary shunt fraction and attenuated the increase in lung wet-to-dry weight ratio seen in the nontreated sheep. Histologically, 7-NI prevented airway obstruction. The increase in airway blood flow after injury in the nontreated group was significantly inhibited by 7-NI. The increase in plasma concentration of nitrate and nitrite (NOx) was inhibited by 7-NI as well. Posttreatment with l-NMMA improved the pulmonary gas exchange, but AG did not. The results of the present study show that nNOS may be involved in the pathogenesis of ALI after smoke inhalation injury followed by bacterial instillation in the airway.
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PMID:Inhibition of neuronal nitric oxide synthase by 7-nitroindazole attenuates acute lung injury in an ovine model. 1276 43

Inhaled nitric oxide (iNO) is a selective pulmonary vasodilator. In randomised trials, iNO increased gas exchange modestly and had no effect on the outcome (survival, chronic lung disease, CLD) in very low birth-weight (VLBW) infants. NO is an important component of the innate immune system and a lipid- soluble free radical scavenger that interacts with the surfactant system. VLBW infants with pneumonia and therapy-resistant, severe respiratory failure soon after birth were studied. Despite their infection, there was no detectable alveolar inducible NO synthase or nitrotyrosine, which is a toxic oxidation product of NO. These infants do not respond to exogenous surfactant and demonstrate severe pulmonary hypertension. However, they require exogenous surfactant prior to iNO. In most cases the disease is complicated by pneumonia and prolonged rupture of fetal membranes. We have shown evidence that iNO given within a few hours after birth reverses the progressive course of respiratory failure and pulmonary hypertension in VLBW infants.
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PMID:Nitric oxide in critical respiratory failure of very low birth weight infants. 1498 Feb 80

The therapeutic effect of a traditional Chinese medicine ren-shen-yang-rong-tang (Japanese name: Ninjin'yoeito, NYT) on murine cytomegalovirus (MCMV)-associated pneumonitis was examined. In MCMV-pneumonitis, IFN-gamma-induced nitric oxide (NO) mediates its pathogenesis. When mice, which had been infected with 0.2LD(50) of MCMV at 28 days previously, were intraperitoneally injected with anti-CD3 monoclonal antibody (mAb), MCMV-pneumonitis was induced in the lung, where high amounts of IFN-gamma-producing cells thereafter accumulated, accompanied by an elevation in the NO level in the serum and abundant expression of inducible NO synthase (iNOS) mRNA, thus resulting in all mice eventually dying. When the mice were orally treated with NYT (1000 mg/kg/day) once on the day of mAb injection and once the day after, the expression level of iNOS-mRNA was suppressed and NO level in the serum decreased. The survival rate improved from 0% to 57.1%. The pathological findings of the lungs in the NYT-treated mice were comparable to those of the uninfected controls. In contrast, NYT itself did not affect either the ratio of IFN-gamma-producing cells or MCMV titer. As a result, NYT had a therapeutic effect on MCMV-pneumonitis by decreasing the degree of inflammation mediated by the IFN-gamma-induced NO. It is also interesting to note that only two oral administrations of NYT had a therapeutic effect on viral disease.
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PMID:Therapeutic effect of a traditional Chinese medicine, ren-shen-yang-rong-tang (Japanese name: Ninjin'yoeito) on nitric oxide-mediated lung injury in a mouse infected with murine cytomegalovirus. 1650 32

Genetic and biochemical data demonstrate a pivotal role for S-nitrosothiols (SNOs) in mediating the actions of nitric oxide synthases (NOSs). SNOs serve to convey NO bioactivity and to regulate protein function. This understanding is of immediate interest to the pulmonary clinical and research communities. This article reviews the following: (1) biochemical and cellular evidence that SNOs in amino acids, peptides, and proteins elicit NOS-dependent signaling in the respiratory system and (2) studies that link SNO signaling to pulmonary medicine. SNO-mediated signaling is involved in the regulation of minute ventilation, ventilation-perfusion matching, pulmonary arterial pressure, basal airway tone, and respiratory and peripheral muscle function. Derangements in SNO signaling are implicated in many disorders relevant to pulmonary and critical care medicine, including apnea, hypoxemia, pulmonary hypertension, asthma, cystic fibrosis, pneumonia, and septic shock.
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PMID:S-nitrosothiol signaling in respiratory biology. 1652 16

Regulation of the inflammatory infiltrate is critical to the successful outcome of pneumonia. Alveolar macrophage apoptosis is a feature of pneumococcal infection and aids disease resolution. The host benefits of macrophage apoptosis during the innate response to bacterial infection are incompletely defined. Because NO is required for optimal macrophage apoptosis during pneumococcal infection, we have explored the role of macrophage apoptosis in regulating inflammatory responses during pneumococcal pneumonia, using inducible NO synthase (iNOS)-deficient mice. iNOS(-/-) mice demonstrated decreased numbers of apoptotic macrophages as compared with wild-type C57BL/6 mice following pneumococcal challenge, greater recruitment of neutrophils to the lung and enhanced expression of TNF-alpha. Pharmacologic inhibition of iNOS produced similar results. Greater pulmonary inflammation was associated with greater levels of early bacteremia, IL-6 production, lung inflammation, and mortality within the first 48 h in iNOS(-/-) mice. Labeled apoptotic alveolar macrophages were phagocytosed by resident macrophages in the lung and intratracheal instillation of exogenous apoptotic macrophages decreased neutrophil recruitment in iNOS(-/-) mice and decreased TNF-alpha mRNA in lungs and protein in bronchial alveolar lavage, as well as chemokines and cytokines including IL-6. These changes were associated with a lower probability of mice becoming bacteremic. This demonstrates the potential of apoptotic macrophages to down-regulate the inflammatory response and for the first time in vivo demonstrates that clearance of apoptotic macrophages decreases neutrophil recruitment and invasive bacterial disease during pneumonia.
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PMID:Decreased alveolar macrophage apoptosis is associated with increased pulmonary inflammation in a murine model of pneumococcal pneumonia. 1705 80

We evaluated the effects of a combined therapy of pre-blockade endogenous nitric oxide synthase (NOS) with N-nitro-L-arginine methyl ester (L-NAME) and continuous inhaled NO (iNO) on the gas exchange and hemodynamics of Escherichia coli pneumonia and sepsis in newborn piglets. Seven to ten day old ventilated newborn piglets were randomized into 5 groups: control, E. coli pneumonia control, pneumonia with iNO 10 ppm, pneumonia pre-treated with L-NAME 10 mg/kg, and pneumonia with the combined therapy of L-NAME pretreatment and iNO. E. coli pneumonia was induced via intratracheal instillation of Escherichia coli, which resulted in progressively decreased cardiac index and oxygen tension; increased pulmonary vascular resistance index (PVRI), intrapulmonary shunting, and developed septicemia at the end of 6 hr experiment. iNO ameliorated the progressive hypoxemia and intrapulmonary shunting without affecting the PVRI. Only two of 8 animals with L-NAME pretreated pneumonia survived. Whereas when iNO was added to infected animals with L-NAME pretreatment, the progressive hypoxemia was abolished as a result of a decrease in intrapulmonary shunting without reverse of the high PVRI and systemic vascular resistance index induced by the L-NAME injection. This result suggests that a NOS blockade may be a possible supportive option for oxygenation by iNO treatment in neonatal Gram-negative bacterial pneumonia and sepsis.
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PMID:Pretreatment with N-nitro-L-arginine methyl ester improved oxygenation after inhalation of nitric oxide in newborn piglets with Escherichia coli pneumonia and sepsis. 1717 70


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