scholarly journals Gender Differences in Low-Molecular-Mass-Induced Acute Lung Inflammation in Mice

2021 ◽  
Vol 22 (1) ◽  
pp. 419
Author(s):  
Yifang Xie ◽  
Dehui Xie ◽  
Bin Li ◽  
Hang Zhao
Keyword(s):  
Gender Differences ◽  
Sex Differences ◽  
Molecular Mass ◽  
Lung Inflammation ◽  
Inflammatory Responses ◽  
Pulmonary Inflammation ◽  
Ovarian Hormones ◽  
Male Mice ◽  
Acute Lung Inflammation ◽  
17Β Estradiol

Gender differences in pulmonary inflammation have been well documented. Although low molecular mass hyaluronan (LMMHA) is known to trigger pulmonary lung inflammation, sex differences in susceptibility to LMMHA are still unknown. In this study, we test the hypothesis that mice may display sex-specific differences after LMMHA administration. After LMMHA administration, male mice have higher neutrophil, cytokine, and chemokine counts compared to that of their female counterparts. Additionally, Ovariectomized (OVX) mice show greater LMMHA-induced inflammation compared to that of mice with intact ovaries. Injections of OVX mice with 17β-estradiol can decrease inflammatory responses in the OVX mice. These results show that ovarian hormones regulate LMMHA induced lung inflammation.

scholarly journals Deletion of Src family kinase Lyn aggravates endotoxin-induced lung inflammation

2015 ◽  
Vol 309 (11) ◽  
pp. L1376-L1381 ◽  
Author(s):  
Rong Gao ◽  
Zhongsen Ma ◽  
Mengshi Ma ◽  
Jinyan Yu ◽  
Jiao Chen ◽  
...  
Keyword(s):  
Tyrosine Kinases ◽  
Lung Inflammation ◽  
Inflammatory Responses ◽  
Pulmonary Inflammation ◽  
Inflammasome Activation ◽  
Inflammatory Signaling ◽  
Endotoxin Challenge ◽  
Proinflammatory Mediators ◽  
Src Family Tyrosine Kinases ◽  
Inhibitory Signaling

Overwhelming acute inflammation often leads to tissue damage during endotoxemia. In the present study, we investigated the role of Lyn, a member of the Src family tyrosine kinases, in modulating inflammatory responses in a murine model of endotoxemia. We examined lung inflammatory signaling in Lyn knockout (Lyn−/−) mice and wild-type littermates (Lyn+/+) during endotoxemia. Our data indicate that Lyn deletion aggravates endotoxin-induced pulmonary inflammation and proinflammatory signaling. We found increased activation of proinflammatory transcription factor NF-κB in the lung tissues of Lyn−/− mice after endotoxin challenge. Furthermore, during endotoxemia, the lung tissues of Lyn−/− mice showed increased inflammasome activation indicated by augmented caspase-1 and IL-1β cleavage and activation. The aggravated lung inflammatory signaling in Lyn−/− mice was associated with increased production of proinflammatory mediators and elevated matrix metallopeptidase 9 and reduced VE-cadherin levels. Our results suggest that Lyn kinase modulates inhibitory signaling to suppress endotoxin-induced lung inflammation.

Regulatory effects of estrogen on acute lung inflammation in mice

2005 ◽  
Vol 288 (4) ◽  
pp. C881-C890 ◽  
Author(s):  
Cecilia L. Speyer ◽  
Nicholas J. Rancilio ◽  
Shannon D. McClintock ◽  
Jeffrey D. Crawford ◽  
Hongwei Gao ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Inflammatory Responses ◽  
Intratracheal Instillation ◽  
Polymorphonuclear Neutrophil ◽  
Myeloperoxidase Activity ◽  
Male Mice ◽  
Acute Lung Inflammation ◽  
End Points ◽  
Female Mice ◽  
Proinflammatory Mediators

The role of estrogen in the regulation of the inflammatory response is not well defined. In this study, we investigated the effects of ovarian hormones on the acute inflammatory response in mouse lungs. Acute lung injury was induced by intratracheal instillation of bacterial lipopolysaccharide (LPS) in male, female, and ovariectomized (OVX) mice. End points of injury were polymorphonuclear neutrophil (PMN) content in bronchoalveolar lavage (BAL) fluids, myeloperoxidase activity in whole lung, and leak of albumin into the lung. After intratracheal instillation of LPS, all end points of injury were substantially increased in male and OVX mice compared with the female mice with intact ovaries. BAL fluids of all mice showed similar levels of chemokines (macrophage inflammatory protein MIP-2, KC, and monocyte chemoattractant proteins MCP-1 and MCP-3) and TNF-α, but enhanced levels of IL-1β were found in OVX and male mice. Serum levels of IL-6 and ICAM-1 levels in lung homogenates from OVX and male mice, compared with those in female mice with intact ovaries, were also enhanced after instillation of LPS. Albumin and PMN content in LPS-injured lungs were reduced to levels found in female mice after administration of estradiol in OVX mice and corresponded to reduced IL-1β, IL-6, and ICAM-1 levels. These data suggest that estrogen suppresses lung inflammatory responses in mice through an effect on vascular cell adhesion molecules and proinflammatory mediators.

scholarly journals Spike protein of SARS‐CoV‐2 activates macrophages and contributes to induction of acute lung inflammation in male mice

2021 ◽  
Vol 35 (9) ◽  
Author(s):  
Xiaoling Cao ◽  
Yan Tian ◽  
Vi Nguyen ◽  
Yuping Zhang ◽  
Chao Gao ◽  
...  
Keyword(s):  
Lung Inflammation ◽  
Spike Protein ◽  
Male Mice ◽  
Acute Lung Inflammation

scholarly journals Myeloid cells control termination of lung inflammation through the NF-κB pathway

2009 ◽  
Vol 296 (3) ◽  
pp. L320-L327 ◽  
Author(s):  
Wei Han ◽  
Myungsoo Joo ◽  
M. Brett Everhart ◽  
John W. Christman ◽  
Fiona E. Yull ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Lung Inflammation ◽  
Inflammatory Responses ◽  
Fetal Liver ◽  
Myeloid Cells ◽  
A549 Cells ◽  
Systemic Infection ◽  
Wild Type ◽  
Acute Lung Inflammation ◽  
Bone Marrow Chimeras

Although acute lung inflammation in response to local or systemic infection involves myeloid and nonmyeloid cells, the interplay between different cell types remains poorly defined. Since NF-κB is a key transcription factor for innate immunity, we investigated whether dysregulated NF-κB activation in myeloid cells impacts inflammatory signaling in nonmyeloid cells and generation of neutrophilic lung inflammation in response to systemic endotoxemia. We generated bone marrow chimeras by fetal liver transplantation of cells deficient in IκBα or p50 into lethally irradiated NF-κB reporter transgenic mice. No differences were apparent between bone marrow chimeras in the absence of an inflammatory stimulus; however, following intraperitoneal injection of Escherichia coli lipopolysaccharide (LPS), IκBα- or p50-deficient bone marrow chimeras showed increased NF-κB activation in nonhematopoietic cells, exaggerated neutrophilic inflammation, and higher mortality compared with untransplanted reporter mice and wild-type bone marrow chimeras. Primary bone marrow-derived macrophages (BMDM) from IκBα−/−or p50−/−exhibited increased NF-κB activation and macrophage inflammatory protein-2 production after LPS treatment compared with wild-type cells, and coculture of BMDM with lung epithelial (A549) cells resulted in increased NF-κB activation in A549 cells and excess IL-8 production by these epithelial cells. These studies indicate an important role for inhibitory members of the NF-κB family acting specifically within myeloid cells to limit inflammatory responses in the lungs.

ADAM-family metalloproteinases in lung inflammation: potential therapeutic targets

2015 ◽  
Vol 308 (4) ◽  
pp. L325-L343 ◽  
Author(s):  
Daniela Dreymueller ◽  
Stefan Uhlig ◽  
Andreas Ludwig
Keyword(s):  
Lung Inflammation ◽  
Inflammatory Responses ◽  
Family Members ◽  
Growth Factor Receptor ◽  
Leukocyte Migration ◽  
Acute Lung Inflammation ◽  
A Cell ◽  
Adam Family ◽  
A Disintegrin And Metalloproteinase ◽  
The Many

Acute and chronic lung inflammation is driven and controlled by several endogenous mediators that undergo proteolytic conversion from surface-expressed proteins to soluble variants by a disintegrin and metalloproteinase (ADAM)-family members. TNF and epidermal growth factor receptor ligands are just some of the many substrates by which these proteases regulate inflammatory or regenerative processes in the lung. ADAM10 and ADAM17 are the most prominent members of this protease family. They are constitutively expressed in most lung cells and, as recent research has shown, are the pivotal shedding enzymes mediating acute lung inflammation in a cell-specific manner. ADAM17 promotes endothelial and epithelial permeability, transendothelial leukocyte migration, and inflammatory mediator production by smooth muscle and epithelial cells. ADAM10 is critical for leukocyte migration and alveolar leukocyte recruitment. ADAM10 also promotes allergic asthma by driving B cell responses. Additionally, ADAM10 acts as a receptor for Staphylococcus aureus ( S. aureus) α-toxin and is crucial for bacterial virulence. ADAM8, ADAM9, ADAM15, and ADAM33 are upregulated during acute or chronic lung inflammation, and recent functional or genetic analyses have linked them to disease development. Pharmacological inhibitors that allow us to locally or systemically target and differentiate ADAM-family members in the lung suppress acute and asthmatic inflammatory responses and S. aureus virulence. These promising results encourage further research to develop therapeutic strategies based on selected ADAMs. These studies need also to address the role of the ADAMs in repair and regeneration in the lung to identify further therapeutic opportunities and possible side effects.

scholarly journals Selective deletion of SHIP-1 in hematopoietic cells in mice leads to severe lung inflammation involving ILC2 cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xujun Ye ◽  
Fengrui Zhang ◽  
Li Zhou ◽  
Yadong Wei ◽  
Li Zhang ◽  
...  
Keyword(s):  
Lung Inflammation ◽  
Airway Remodeling ◽  
Pulmonary Inflammation ◽  
Hematopoietic Cells ◽  
Cell Lineage ◽  
Allergic Inflammation ◽  
Cell Types ◽  
Lymphoid Cells ◽  
Whole Body

AbstractSrc homology 2 domain–containing inositol 5-phosphatase 1 (SHIP-1) regulates the intracellular levels of phosphotidylinositol-3, 4, 5-trisphosphate, a phosphoinositide 3–kinase (PI3K) product. Emerging evidence suggests that the PI3K pathway is involved in allergic inflammation in the lung. Germline or induced whole-body deletion of SHIP-1 in mice led to spontaneous type 2-dominated pulmonary inflammation, demonstrating that SHIP-1 is essential for lung homeostasis. However, the mechanisms by which SHIP-1 regulates lung inflammation and the responsible cell types are still unclear. Deletion of SHIP-1 selectively in B cells, T cells, dendritic cells (DC) or macrophages did not lead to spontaneous allergic inflammation in mice, suggesting that innate immune cells, particularly group 2 innate lymphoid cells (ILC2 cells) may play an important role in this process. We tested this idea using mice with deletion of SHIP-1 in the hematopoietic cell lineage and examined the changes in ILC2 cells. Conditional deletion of SHIP-1 in hematopoietic cells in Tek-Cre/SHIP-1 mice resulted in spontaneous pulmonary inflammation with features of type 2 immune responses and airway remodeling like those seen in mice with global deletion of SHIP-1. Furthermore, when compared to wild-type control mice, Tek-Cre/SHIP-1 mice displayed a significant increase in the number of IL-5/IL-13 producing ILC2 cells in the lung at baseline and after stimulation by allergen Papain. These findings provide some hints that PI3K signaling may play a role in ILC2 cell development at baseline and in response to allergen stimulation. SHIP-1 is required for maintaining lung homeostasis potentially by restraining ILC2 cells and type 2 inflammation.

scholarly journals Combined In Vitro and In Vivo Approaches to Propose a Putative Adverse Outcome Pathway for Acute Lung Inflammation Induced by Nanoparticles: A Study on Carbon Dots

Nanomaterials ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 180
Author(s):  
Maud Weiss ◽  
Jiahui Fan ◽  
Mickaël Claudel ◽  
Luc Lebeau ◽  
Françoise Pons ◽  
...  
Keyword(s):  
Carbon Dots ◽  
Lung Inflammation ◽  
Adverse Outcome ◽  
Cellular Responses ◽  
Target Cells ◽  
Inflammasome Activation ◽  
Adverse Outcome Pathway ◽  
Acute Lung Inflammation

With the growth of nanotechnologies, concerns raised regarding the potential adverse effects of nanoparticles (NPs), especially on the respiratory tract. Adverse outcome pathways (AOP) have become recently the subject of intensive studies in order to get a better understanding of the mechanisms of NP toxicity, and hence hopefully predict the health risks associated with NP exposure. Herein, we propose a putative AOP for the lung toxicity of NPs using emerging nanomaterials called carbon dots (CDs), and in vivo and in vitro experimental approaches. We first investigated the effect of a single administration of CDs on mouse airways. We showed that CDs induce an acute lung inflammation and identified airway macrophages as target cells of CDs. Then, we studied the cellular responses induced by CDs in an in vitro model of macrophages. We observed that CDs are internalized by these cells (molecular initial event) and induce a series of key events, including loss of lysosomal integrity and mitochondrial disruption (organelle responses), as well as oxidative stress, inflammasome activation, inflammatory cytokine upregulation and macrophage death (cellular responses). All these effects triggering lung inflammation as tissular response may lead to acute lung injury.

scholarly journals Administration route governs the therapeutic efficacy, biodistribution and macrophage targeting of anti-inflammatory nanoparticles in the lung

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Lu Wang ◽  
Yafei Rao ◽  
Xiali Liu ◽  
Liya Sun ◽  
Jiameng Gong ◽  
...  
Keyword(s):  
Therapeutic Efficacy ◽  
Lung Inflammation ◽  
Respiratory Diseases ◽  
Inflammatory Responses ◽  
The Other ◽  
Target Cells ◽  
Administration Route ◽  
Toll Like Receptor ◽  
Administration Routes ◽  
Anti Inflammatory

Abstract Background Uncontrolled inflammation is a central problem for many respiratory diseases. The development of potent, targeted anti-inflammatory therapies to reduce lung inflammation and re-establish the homeostasis in the respiratory tract is still a challenge. Previously, we developed a unique anti-inflammatory nanodrug, P12 (made of hexapeptides and gold nanoparticles), which can attenuate Toll-like receptor-mediated inflammatory responses in macrophages. However, the effect of the administration route on its therapeutic efficacy and tissue distribution remained to be defined. Results In this study, we systematically compared the effects of three different administration routes [the intratracheal (i.t.), intravenous (i.v.) and intraperitoneal (i.p.)] on the therapeutic activity, biodistribution and pulmonary cell targeting features of P12. Using the LPS-induced ALI mouse model, we found that the local administration route via i.t. instillation was superior in reducing lung inflammation than the other two routes even treated with a lower concentration of P12. Further studies on nanoparticle biodistribution showed that the i.t. administration led to more accumulation of P12 in the lungs but less in the liver and other organs; however, the i.v. and i.p. administration resulted in more nanoparticle accumulation in the liver and lymph nodes, respectively, but less in the lungs. Such a lung favorable distribution was also determined by the unique surface chemistry of P12. Furthermore, the inflammatory condition in the lung could decrease the accumulation of nanoparticles in the lung and liver, while increasing their distribution in the spleen and heart. Interestingly, the i.t. administration route helped the nanoparticles specifically target the lung macrophages, whereas the other two administration routes did not. Conclusion The i.t. administration is better for treating ALI using nanodevices as it enhances the bioavailability and efficacy of the nanodrugs in the target cells of the lung and reduces the potential systematic side effects.

scholarly journals Development-Dependent Plasticity in Vasoactive Intestinal Polypeptide Neurons in the Infralimbic Cortex

2021 ◽  
Vol 2 (1) ◽  
Author(s):  
Stuart A Collins ◽  
Ipe Ninan
Keyword(s):  
Sex Differences ◽  
Anxiety Disorders ◽  
Vasoactive Intestinal Polypeptide ◽  
Cortical Plasticity ◽  
Male Mice ◽  
Infralimbic Cortex ◽  
Membrane Excitability ◽  
Gabaergic Transmission ◽  
Intestinal Polypeptide

Abstract The onset of several neuropsychiatric disorders including anxiety disorders coincides with adolescence. Consistently, threat extinction, which plays a key role in the regulation of anxiety-related behaviors, is diminished during adolescence. Furthermore, this attenuated threat extinction during adolescence is associated with an altered synaptic plasticity in the infralimbic medial prefrontal cortex (IL-mPFC), a brain region critical for threat extinction. However, the mechanism underlying the altered plasticity in the IL-mPFC during adolescence is unclear. Given the purported role of vasoactive intestinal polypeptide expressing interneurons (VIPINs) in disinhibition and hence their potential to affect cortical plasticity, we examined whether VIPINs exhibit an adolescence-specific plasticity in the IL-mPFC. We observed an increase in GABAergic transmission and a decrease in excitability in VIPINs during adolescence. Male mice show a significantly higher VIPIN-pyramidal neuron GABAergic transmission compared with female mice. The observed increase in GABAergic transmission and a decrease in membrane excitability in VIPINs during adolescence could play a role in the altered plasticity in the adolescent IL-mPFC. Furthermore, the suppression of VIPIN-mediated GABAergic transmission in females might be relevant to sex differences in anxiety disorders.

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