Amelioration of airway inflammation and pulmonary edema by Teucrium stocksianum via attenuation of pro-inflammatory cytokines and up-regulation of AQP1 and AQP5

Background: Airway smooth muscle (ASM) is considered to be a target for mediators released during airway inflammation.Aims: To investigate the expression of c-fos, a constituent of the transcription factor activator protein-1, in human ASM cells. In addition, to measure the release of interleukin (IL)-6 into the conditioned medium of stimulated ASM cells, as well as DNA biosynthesis and changes in cell number.Methods: Serum-deprived human ASM cells in the G0/G1phase were stimulated with the pro-inflammatory cytokines; tumour necrosis factor-α, IL-1β, IL-5 and IL-6. The expression of mRNA encoding the proto-oncogene c-fos was measured by Northern blot analysis. Cell proliferation was assessed by {3H}-thymidine incorporation assays and cell counting, and IL-6 levels in cell-conditioned medium were measured by enzyme-linked immunosorbent assay.Results: All of the cytokines investigated induced a rapid (within 1h) and transient increase in the expression of mRNA encoding c-fos, followed by the expression and enhanced release of IL-6. Cell proliferation remained unchanged in cytokine-stimulated cells.Conclusions: Cytokine-induced c-fos expression in human ASM cells could be described as a marker of cell ‘activation'. The possible association of these results with airway inflammation, through secondary intracellular mechanisms such as cytokine production, is discussed.

Download Full-text

Knockout of Formyl Peptide Receptor-1 Attenuates Cigarette Smoke–Induced Airway Inflammation in Mice

Frontiers in Pharmacology ◽

10.3389/fphar.2021.632225 ◽

2021 ◽

Vol 12 ◽

Author(s):

Lijuan Gao ◽

Ni Zeng ◽

Zhicheng Yuan ◽

Tao Wang ◽

Lei Chen ◽

...

Keyword(s):

Western Blot ◽

Airway Inflammation ◽

Inflammatory Cytokines ◽

Bioinformatics Analysis ◽

Formyl Peptide Receptor ◽

Wild Type ◽

Peptide Receptor ◽

Formyl Peptide ◽

Gene Study ◽

Pro Inflammatory Cytokines

Objective: The formyl peptide receptor-1 (FPR-1) has been reported to be implicated in the regulation of inflammatory disorders, while its role in cigarette smoke (CS)–induced airway inflammation has not been fully explained. In this study, we investigated the role of FPR-1 in CS-induced airway inflammation and the possible mechanism through gene knockout (KO) technology and transcriptional study.Methods: FPR-1 KO or wild-type C57BL/6 mice were exposed to mainstream CS to establish an airway inflammation model. Cell counts and pro-inflammatory cytokines were measured in bronchoalveolar lavage fluid (BALF). Lung tissues were collected for histological examination, polymerase chain reaction, Western blot, transcriptomic gene study, and related bioinformatics analysis.Results: CS exposure induced significant histological inflammatory changes, increased neutrophils, and pro-inflammatory cytokines in the BALF of wild-type mice, which were all attenuated by KO of FPR-1. The transcriptomic gene study showed a total of 198 up-regulated genes and 282 down-regulated genes in mouse lungs. Bioinformatics analysis including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) suggested these differentiated expressed genes were significantly related to the immune, chemotaxis responses, and cross-talked with a complicated network of signaling pathways including NF-κB. Western blot validated that KO of FPR-1 inhibited CS-induced NF-κB activation.Conclusion: Knockout of FPR-1 significantly ameliorates CS-induced airway inflammation in mice, possibly via its related immune-chemotaxis responses and inhibition of NF-κB activation.

Download Full-text

Acute Hyperglycemia Aggravates Lung Injury via Activation of the SGK1–NKCC1 Pathway

International Journal of Molecular Sciences ◽

10.3390/ijms21134803 ◽

2020 ◽

Vol 21 (13) ◽

pp. 4803

Author(s):

Chin-Pyng Wu ◽

Kun-Lun Huang ◽

Chung-Kan Peng ◽

Chou-Chin Lan

Keyword(s):

Lung Injury ◽

Pulmonary Edema ◽

Inflammatory Cytokines ◽

Glucose Solution ◽

Alveolar Cells ◽

Severe Hypoxemia ◽

Sodium Potassium ◽

Acute Hyperglycemia ◽

Pro Inflammatory Cytokines ◽

Severe Lung

Acute lung injury (ALI) is characterized by severe hypoxemia and has significantly high mortality rates. Acute hyperglycemia occurs in patients with conditions such as sepsis or trauma, among others, and it results in aggravated inflammation and induces damage in patients with ALI. Regulation of alveolar fluid is essential for the development and resolution of pulmonary edema in lung injury. Pulmonary sodium-potassium-chloride co-transporter 1 (NKCC1) regulates the net influx of ions and water into alveolar cells. The activation of with-no-lysine kinase 4 (WNK4), STE20/SPS1-related proline/alanine rich kinase (SPAK) and the NKCC1 pathway lead to an increase in the expression of NKCC1 and aggravation of ALI. Moreover, hyperglycemia is known to induce NKCC1 expression via the activation of the serum-glucocorticoid kinase 1 (SGK1)–NKCC1 pathway. We aim to evaluate the influence of acute hyperglycemia on the SGK1–NKCC1 pathway in ALI. ALI was induced using a high tidal volume for four hours in a rat model. Acute hyperglycemia was induced by injection with 0.5 mL of 40% glucose solution followed by continuous infusion at 2 mL/h. The animals were divided into sham, sham+ hyperglycemia, ALI, ALI + hyperglycemia, ALI + inhaled bumetanide (NKCC1 inhibitor) pretreatment, ALI + hyperglycemia + inhalational bumetanide pretreatment, and ALI + hyperglycemia + post-ALI inhalational bumetanide groups. Severe lung injury along with pulmonary edema, alveolar protein leakage, and lung inflammation was observed in ALI with hyperglycemia than in ALI without hyperglycemia. This was concurrent with the higher expression of pro-inflammatory cytokines, infiltration of neutrophils and alveolar macrophages (AM) 1, and NKCC1 expression. Inhalational NKCC1 inhibitor significantly inhibited the SGK1–NKCC1, and WNK4–SPAK–NKCC1 pathways. Additionally, it reduced pulmonary edema, inflammation, levels of pro-inflammatory cytokines, neutrophils and AM1 and increased AM2. Therefore, acute hyperglycemia aggravates lung injury via the further activation of the SGK1–NKCC1 pathway. The NKCC1 inhibitor can effectively attenuate lung injury aggravated by acute hyperglycemia.

Download Full-text

Transient Leukocytopenia Associated with a Steep Surge of Pro-inflammatory Cytokines in a Patient with Severe Cardiogenic Pulmonary Edema

Internal Medicine ◽

10.2169/internalmedicine.45.6088 ◽

2006 ◽

Vol 45 (20) ◽

pp. 1153-1155 ◽

Cited By ~ 1

Author(s):

Takeshi Yamamoto ◽

Katsuyuki Terajima ◽

Koji Kato ◽

Yu-ki Iwasaki ◽

Yasuo Miyagi ◽

...

Keyword(s):

Pulmonary Edema ◽

Inflammatory Cytokines ◽

Cardiogenic Pulmonary Edema ◽

Pro Inflammatory Cytokines

Download Full-text

Surfactant Attenuates Air Embolism-Induced Lung Injury by Suppressing NKCC1 Expression and NF-κB Activation

Inflammation ◽

10.1007/s10753-020-01266-1 ◽

2020 ◽

Author(s):

Chou-Chin Lan ◽

Yao-Kuang Wu ◽

Chung-Kan Peng ◽

Kun-Lun Huang ◽

Chin-Pyng Wu

Keyword(s):

Lung Injury ◽

Pulmonary Edema ◽

Inflammatory Cytokines ◽

Lung Inflammation ◽

Inflammatory Responses ◽

Air Embolism ◽

Lower Surface ◽

Beneficial Effects ◽

Pro Inflammatory Cytokines

Abstract Excessive amounts of air can enter the lungs and cause air embolism (AE)-induced acute lung injury (ALI). Pulmonary AE can occur during diving, aviation, and iatrogenic invasive procedures. AE-induced lung injury presents with severe hypoxia, pulmonary hypertension, microvascular hyper-permeability, and severe inflammatory responses. Pulmonary AE-induced ALI is a serious complication resulting in significant morbidity and mortality. Surfactant is abundant in the lungs and its function is to lower surface tension. Earlier studies have explored the beneficial effects of surfactant in ALI; however, none have investigated the role of surfactant in pulmonary AE-induced ALI. Therefore, we conducted this study to determine the effects of surfactant in pulmonary AE-induced ALI. Isolated-perfused rat lungs were used as a model of pulmonary AE. The animals were divided into four groups (n = 6 per group): sham, air embolism (AE), AE + surfactant (0.5 mg/kg), and AE+ surfactant (1 mg/kg). Surfactant pretreatment was administered before the induction of pulmonary AE. Pulmonary AE was induced by the infusion of 0.7 cc air through a pulmonary artery catheter. After induction of air, pulmonary AE was presented with pulmonary edema, pulmonary microvascular hyper-permeability, and lung inflammation with neutrophilic sequestration. Activation of NF-κB was observed, along with increased expression of pro-inflammatory cytokines, and Na-K-Cl cotransporter isoform 1 (NKCC1). Surfactant suppressed the activation of NF-κB and decreased the expression of pro-inflammatory cytokines and NKCC1, thereby attenuating AE-induced lung injury. Therefore, AE-induced ALI presented with pulmonary edema, microvascular hyper-permeability, and lung inflammation. Surfactant suppressed the expressions of NF-κB, pro-inflammatory cytokines, and NKCC1, thereby attenuating AE-induced lung injury.

Download Full-text

Banhahubak-Tang Tablet, a Standardized Medicine Attenuates Allergic Asthma via Inhibition of Janus Kinase 1 (JAK1)/ Signal Transducer and Activator of Transcription 6 (STAT6) Signal Pathway

Molecules ◽

10.3390/molecules25092206 ◽

2020 ◽

Vol 25 (9) ◽

pp. 2206 ◽

Cited By ~ 1

Author(s):

Yeon Kyung Nam ◽

Seong Chul Jin ◽

Mi Hye Kim ◽

La Yoon Choi ◽

Yong-Bok Lee ◽

...

Keyword(s):

Airway Inflammation ◽

Allergic Asthma ◽

Inflammatory Cytokines ◽

Inflammatory Cells ◽

Janus Kinase ◽

Total Serum ◽

Therapeutic Effects ◽

Signal Transducer ◽

Janus Kinase 1 ◽

Pro Inflammatory Cytokines

Exposure to particulate matter (PM) has been known to be one of the risk factors to cause allergic asthma, leading to development of respiratory disease. Banhahubak-tang tablet (BHT), a standardized Korean Medicine, is prescribed for neurasthenia, laryngopharyngitis and asthma. In this study, we investigated therapeutic effects of BHT on airway inflammation in ovalbumin (OVA) and PM smaller than 10 μm (PM10)-induced allergic asthma mice. To establish allergic asthma with airway hyper-responsiveness by PM10, BALB/c mice were sensitized and challenged with OVA and PM10, and orally administered BHT. Histological staining was performed to assess airway remodeling. Serum and bronchoalveolar lavage fluid (BALF) was collected for measuring immunoglobulin levels and counting inflammatory cells, respectively. Expression levels of Janus kinase 1 (JAK1)/signal transducer and activator of transcription 6 (STAT6), pro-inflammatory cytokines and type 2 T-helper (Th2)-related cytokines were analyzed in vivo and in vitro models. Histopathological analysis demonstrated that BHT suppressed inflammatory cell infiltration, mucus hypersecretion and collagen deposition in the airway. BHT administration effectively decreased number of inflammatory cells in BALF. BHT reduced total serum Immunoglobulin E (IgE) and Immunoglobulin G (IgG) levels. In addition, BHT significantly inhibited the phosphorylation of JAK1 and STAT6 expressions. Release of pro-inflammatory cytokines and Th2-related cytokines were down-regulated by BHT. In conclusion, BHT mitigated airway inflammation by down-regulating pro-inflammatory and Th2-related cytokines via JAK1/STAT6 signaling. BHT might be a promising herbal medicine for preventing airway inflammation. Moreover, an intervention study among humans is needed to further evaluate the possible beneficial effects of BHT in allergic asthma.

Download Full-text

Cytokine synergy, collagenases and cartilage collagen breakdown

Biochemical Society Symposium ◽

10.1042/bss0700125 ◽

2003 ◽

Vol 70 ◽

pp. 125-133 ◽

Cited By ~ 7

Author(s):

Tim E. Cawston ◽

Jenny M. Milner ◽

Jon B. Catterall ◽

Andrew D. Rowan

Keyword(s):

Matrix Metalloproteinases ◽

Inflammatory Cytokines ◽

Activator Protein 1 ◽

Activator Protein ◽

And Cartilage ◽

Pro Inflammatory Cytokines

We have investigated proteinases that degrade cartilage collagen. We show that pro-inflammatory cytokines act synergistically with oncastatin M to promote cartilage collagen resorption by the up-regulation and activation of matrix metalloproteinases (MMPs). The precise mechanisms are not known, but involve the up-regulation of c-fos, which binds to MMP promoters at a proximal activator protein-1 (AP-1) site. This markedly up-regulates transcription and leads to higher levels of active MMP proteins.

Download Full-text