Airway hyperresponsiveness induced by repetitive intraperitoneal injection of lipopolysacharide and the involvement of inflammation and nitric oxide in guinea pigs

Jiang, Huai; Jian, Qu; He, Ling; Pan, Jue; Chen, X.; Li, L.; Zhu, Dawei; Cao, Yunxia

doi:10.1007/s00011-006-0085-x

Cited by 10 publications

(5 citation statements)

References 37 publications

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“…iNOS expression is upregulated by various proinflammatory signals, resulting in elevations in NO concentrations ( Hesslinger et al, 2009 ). NO production, an active player in the respiratory system and disease, is considered a potential mediator of airway responsiveness ( Jiang et al, 2006 ). In this study, CS and LPS exposed mice exhibited marked increases in MMP-9 and iNOS expression in lung tissue, which were accompanied by elevations in the phosphorylation of NF-κB and IκBα.…”

Section: Discussionmentioning

confidence: 99%

So-Cheong-Ryoung-Tang Attenuates Pulmonary Inflammation Induced by Cigarette Smoke in Bronchial Epithelial Cells and Experimental Mice

et al. 2018

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So-Cheong-Ryoung-Tang is a traditionally used herbal formula for the treatment of pulmonary diseases in China, Korea, and Japan. We investigated the protective effects of So-Cheong-Ryong-Tang water extract (SCWE) in cigarette smoke concentrate (CSC) stimulated human airway epithelial cell line NCI-H292 and mice exposed cigarette smoke (CS) and lipopolysaccharide (LPS). In the CSC-stimulated NCI-H292 cells, SCWE inhibited proinflammatory cytokines in a concentration-dependent manner, as evidenced by a reduction in their mRNA levels. Also, SCWE significant reduced inducible nitric oxide synthase (iNOS) expression and nuclear factor kappa B (NF-κB) phosphorylation in CSC-stimulated cells. The mice were exposed to CS for 1 h per day (a total of eight cigarettes per day) for 7 days and received LPS intranasally on day 5. The mice were administered a dose of SCWE (100 and 200 mg/kg) 1 h before CS exposure. In in vivo, SCWE decreased the inflammatory cell count and reduced the expression of the proinflammatory cytokines in the broncho-alveolar lavage fluid (BALF) compared with CS and LPS exposed mice. SCWE attenuated inflammatory cell infiltration in airway induced by CS and LPS exposure, and this decrease was accompanied by a reduction in the expression levels of iNOS and MMP-9 in lung tissue. The extract also inhibited the phosphorylation of inhibitor of kappa B alpha (IκBα) and NF-κB induced by CS and LPS exposure in lung tissue. These results suggest that SCWE may effectively inhibit airway inflammatory responses induced by CS and LPS exposure via the NF-κB pathway. Therefore, SCWE may be a potential treatment for airway inflammatory diseases, such as chronic obstructive pulmonary disease (COPD).

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Section: Discussionmentioning

confidence: 99%

So-Cheong-Ryoung-Tang Attenuates Pulmonary Inflammation Induced by Cigarette Smoke in Bronchial Epithelial Cells and Experimental Mice

et al. 2018

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“…This agrees with a study by Jiang et al . ( 2006 ) who showed a transient increase in neutrophils following i.p. administration of LPS.…”

Section: Discussionmentioning

confidence: 99%

LPS exacerbates functional and inflammatory responses to ovalbumin and decreases sensitivity to inhaled fluticasone propionate in a guinea pig model of asthma

Lowe

Thomas

Nials

et al. 2015

British J Pharmacology

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Background and PurposeAsthma exacerbations contribute to corticosteroid insensitivity. LPS is ubiquitous in the environment. It causes bronchoconstriction and airway inflammation and may therefore exacerbate allergen responses. This study examined whether LPS and ovalbumin co-administration could exacerbate the airway inflammatory and functional responses to ovalbumin in conscious guinea pigs and whether these exacerbated responses were insensitive to inhaled corticosteroid treatment with fluticasone propionate (FP).Experimental ApproachGuinea pigs were sensitized and challenged with ovalbumin and airway function recorded as specific airway conductance by whole body plethysmography. Airway inflammation was measured from lung histology and bronchoalveolar lavage. Airway hyper-reactivity (AHR) to inhaled histamine was examined 24 h after ovalbumin. LPS was inhaled alone or 24 or 48 h before ovalbumin and combined with ovalbumin. FP (0.05–1 mg·mL−1) or vehicle was nebulized for 15 min twice daily for 6 days before ovalbumin or LPS exposure.Key ResultsOvalbumin inhalation caused early (EAR) and late asthmatic response (LAR), airway hyper-reactivity to histamine and influx of inflammatory cells into the lungs. LPS 48 h before and co-administered with ovalbumin exacerbated the response with increased length of the EAR, prolonged response to histamine and elevated inflammatory cells. FP 0.5 and 1 mg·mL−1 reduced the LAR, AHR and cell influx with ovalbumin alone, but was ineffective when guinea pigs were exposed to LPS before and with ovalbumin.Conclusions and ImplicationsLPS exposure exacerbates airway inflammatory and functional responses to allergen inhalation and decreases corticosteroid sensitivity. Its widespread presence in the environment could contribute to asthma exacerbations and corticosteroid insensitivity in humans.

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“…LPS has been demonstrated to increase iNOS and decrease cNOS activities in airways (Jiang et al, 2006;Tulić et al, 2001). NO decreases ENaC open probability through the production of cGMP (Eaton et al, 2008;Matalon et al, 2003) and inhibits the activity of the Na + ,K + -pump by triggering its endocytosis and internalization from the basolateral membrane , However, our earlier findings indicate that LPS increased, rather than decreased, Na + ,K + -pump activity and expression.…”

Section: Alternative Pathways Involved In Enac and Na + K + -Pump Accontrasting

confidence: 54%

“…We measured COX-2 transcription because our earlier observation that indomethacin also inhibited modestly the hyperpolarizing effect of LPS indicated a role of increased prostaglandin production by COX-1/2 . Since NO has been linked with airway hyperreactivity (Jiang et al, 2006) and inhibition of the Na + ,K + -pump , we measured ~ 97 ~ both eNOS and iNOS. IL-1β was measured because it has been observed to increase the expression of both the ENaC and the Na + ,K + -pump (Ye et al, 2004).…”

Section: Lps Does Not Affect the Transcription Of αEnac And α 1 Na + mentioning

confidence: 99%

Systemic lipopolysaccharide stimulates airway transepithelial Na+ transport by increasing ENaC and Na+,K+ -pump activity

Dodrill¹

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Systemic lipopolysaccharide stimulates airway transepithelial Na + transport by increasing ENaC and Na + ,K +-pump activity Michael W. Dodrill Our laboratory found that systemic administration of lipopolysaccharide (LPS; 4 mg/kg) hyperpolarized the transepithelial potential difference (V t) of tracheal epithelium in the isolated, perfused trachea (IPT) of the guinea pig 18 h after injection. We hypothesized that LPS stimulates the transepithelial movement of Na + via the epithelial sodium channel (ENaC)/Na + ,K +-pump axis, leading to hyperpolarization of V t. LPS increased the V t response to amiloride, i.e., offset the effect of LPS, indicating that Na + transport was increased. The functional activity of ENaC was measured in the IPT after short-circuiting the Na + ,K +-pump with basolateral amphotericin B. LPS had no effect on the hyperpolarization response to apical trypsin in the Ussing chamber, indicating that channel activating proteases are not involved in the LPS-induced activation of ENaC. To assess Na + ,K +-pump activity in the IPT, ENaC was short-circuited with apical amphotericin B. The greater V t in the presence of amphotericin B in tracheas from LPS-treated animals compared to controls revealed that LPS increased Na + ,K +-pump activity. This finding was confirmed in the Ussing chamber by inhibiting the Na + ,K +-pump via extracellular K + removal, loading the epithelium with Na + , and observing a greater hyperpolarization response to K + restoration. Using qPCR, the effects of LPS on the transcription of αENaC, α 1 Na + ,K +pump, COX-2, eNOS, iNOS, IL-1β, and TNF-α were measured at 3 and 18 h. In the epithelium, LPS increased the transcription of COX-2, IL-1β, and, to nonsignificant extent, TNF-α at 3 h, but not at 18 h. In alveolar macrophages, TNF-α, and, to a nonsignificant extent, COX-2 and IL-1β were up-regulated at 3 h, but not at 18 h. Even though LPS stimulated the transcription of some genes, αENaC and α 1 Na + ,K +-ATPase transcription were not affected. The expression of α-, β-, and γ-ENaC and α 1 Na + ,K +-pump from tracheal epithelium and kidney cortex/medulla were investigated by western blotting. All three ENaC subunits were detected as cleavage fragments, yet LPS had no effect on their expression. LPS increased the expression of the α 1 subunit and the α 1-, α 2-, and α 3-subunits, collectively, of the Na + ,K +-pump. Taken together, the findings of this study reveal that LPS hyperpolarizes the airway epithelium by increasing the activities of ENaC and the Na + ,K +-pump. ENaC activation by LPS is not accomplished via a change in ENaC regulation involving proteolytic cleavage. LPS increases Na + transport downstream of the genetic level, in part, by stimulating the expression of the Na + ,K +-pump.

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Airway hyperresponsiveness induced by repetitive intraperitoneal injection of lipopolysacharide and the involvement of inflammation and nitric oxide in guinea pigs

Abstract: Our results demonstrate that repetitive intraperitoneal LPS can induce persistent AHR which occurs earlier when the frequency of injection increase, and an elevation of NO production and iNOS activity may be involved in is systemic-LPS-induced AHR.

Cited by 10 publications

References 37 publications

So-Cheong-Ryoung-Tang Attenuates Pulmonary Inflammation Induced by Cigarette Smoke in Bronchial Epithelial Cells and Experimental Mice

So-Cheong-Ryoung-Tang Attenuates Pulmonary Inflammation Induced by Cigarette Smoke in Bronchial Epithelial Cells and Experimental Mice

LPS exacerbates functional and inflammatory responses to ovalbumin and decreases sensitivity to inhaled fluticasone propionate in a guinea pig model of asthma

Systemic lipopolysaccharide stimulates airway transepithelial Na+ transport by increasing ENaC and Na+,K+ -pump activity

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