Immunotherapy strategies and prospects for acute lung injury: Focus on immune cells and cytokines

Zhu, Wen; Zhang, Yiwen; Wang, Yinghong

doi:10.3389/fphar.2022.1103309

Cited by 12 publications

(7 citation statements)

References 119 publications

(124 reference statements)

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“…Sepsis is a severe infectious complication, where immune dysfunction is implicated in pathogenesis. Growing evidence suggests that metabolic impairment in immune cells like macrophages, leading to immune dysfunction, are closely associated with sepsis ( 2 - 4 ). Mitochondria are the major sites of cellular energy metabolism, and mitochondrial dysfunction directly contributes to aberrant immune cell responses ( 21 , 22 ).…”

Section: Discussionmentioning

confidence: 99%

“…Sepsis is a medical condition characterized by life-threatening organ dysfunction resulting from an abnormal and uncontrolled response of the body to an infection, and represents a major global public health problem ( 1 ). The lungs are particularly vulnerable to sepsis, and ensuing pulmonary dysfunction can culminate in acute lung injury (ALI) or even acute respiratory distress syndrome ( 1 - 4 ). Despite rapid advances in antimicrobial therapy and organ support, mortality from sepsis-induced ALI remains high.…”

Section: Introductionmentioning

confidence: 99%

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Upregulation of PGC-1α expression by pioglitazone mediates prevention of sepsis-induced acute lung injury

Tang,

Dong,

Wang

et al. 2024

Braz J Med Biol Res

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The imbalance between pro-inflammatory M1 and anti-inflammatory M2 macrophages plays a critical role in the pathogenesis of sepsis-induced acute lung injury (ALI). Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) may modulate macrophage polarization toward the M2 phenotype by altering mitochondrial activity. This study aimed to investigate the role of the PGC-1α agonist pioglitazone (PGZ) in modulating sepsis-induced ALI. A mouse model of sepsis-induced ALI was established using cecal ligation and puncture (CLP). An in vitro model was created by stimulating MH-S cells with lipopolysaccharide (LPS). qRT-PCR was used to measure mRNA levels of M1 markers iNOS and MHC-II and M2 markers Arg1 and CD206 to evaluate macrophage polarization. Western blotting detected expression of peroxisome proliferator-activated receptor gamma (PPARγ) PGC-1α, and mitochondrial biogenesis proteins NRF1, NRF2, and mtTFA. To assess mitochondrial content and function, reactive oxygen species levels were detected by dihydroethidium staining, and mitochondrial DNA copy number was measured by qRT-PCR. In the CLP-induced ALI mouse model, lung tissues exhibited reduced PGC-1α expression. PGZ treatment rescued PGC-1α expression and alleviated lung injury, as evidenced by decreased lung wet-to-dry weight ratio, pro-inflammatory cytokine secretion (tumor necrosis factor-α, interleukin-1β, interleukin-6), and enhanced M2 macrophage polarization. Mechanistic investigations revealed that PGZ activated the PPARγ/PGC-1α/mitochondrial protection pathway to prevent sepsis-induced ALI by inhibiting M1 macrophage polarization. These results may provide new insights and evidence for developing PGZ as a potential ALI therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Upregulation of PGC-1α expression by pioglitazone mediates prevention of sepsis-induced acute lung injury

Tang,

Dong,

Wang

et al. 2024

Braz J Med Biol Res

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“…It should be noted that this type of excessive response was elicited by PTX3 and SS2 strain HA9801 in concert, with the overuse of CPS2 extraction causing a significant increase in mortality when the mice were co-treated with PTX3 at a fixed dose (20 μg/mouse). Indeed, exaggerated inflammatory responses can contribute to tissue damage and immunopathology [ 38 , 39 ], resulting in terrifying inflammatory storms and even death. A similar observation has also been demonstrated in Klebsiella pneumoniae : the overexpression of PTX3 in mice given a low dose of bacteria promoted resistance to K. pneumoniae respiratory infection, while in mice given a high inoculum, overexpression of PTX3 was associated with faster lethality.…”

Section: Discussionmentioning

confidence: 99%

Host PTX3 Protein and Bacterial Capsule Coordinately Regulate the Inflammatory Response during Streptococcus suis Infection

Bai

Fan

Zhong

et al. 2023

Veterinary Sciences

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Streptococcus suis serotype 2 (SS2) is a noteworthy zoonotic pathogen that has been responsible for large economic losses in pig production and a great threat to human health. Pentraxin 3 (PTX3) is an essential regulator of the innate immune response to bacterial pathogens; however, its role during SS2 infection is not fully understood. In this study, we found that the SS2 strain HA9801 induced a significant inflammatory response in the mouse air pouch model; this response was amplified by the treatment of exogenous PTX3 simultaneously in terms of the results of inflammatory cell recruitment and proinflammatory cytokine IL-6 production. In addition, PTX3 facilitated the phagocytosis of macrophage Ana-1 against SS2 strain HA9801. The supplementation of exogenous PTX3 significantly reduced the bacterial loads in a dose-dependent manner in lungs, livers and bloods of SS2-infected mice compared to the samples with HA9801 infection alone; this finding indicated that PTX3 may facilitate the bacterial clearance through enhancing the host inflammatory response during SS2 infection. Both PTX3 and SS2 capsular polysaccharide (CPS2) were required for the robust inflammatory response, implying that the host PTX3 protein and SS2 surface CPS2 modulate the host innate immune response in concert. All of these results suggested that PTX3 is a potential novel biological agent for the SS2 infection; however, the recommended dose of PTX3 must be evaluated strictly to avoid inducing an excessive inflammatory response that can cause serious tissue injury and animal death.

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“…It has various causes, including severe infection, trauma, and the inhalation of harmful substances. Uncontrolled in ammatory responses, continuous production of proin ammatory factors, and mass death of lung epithelial cells result in the loss of alveolar integrity and increase the permeability of lung capillaries [32].…”

Section: Discussionmentioning

confidence: 99%

Morin improves LPS-induced acute lung injury by inhibiting pyroptosis and inflammatory response of macrophages

Nie

Feng

Zhang

et al. 2023

Preprint

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Acute lung injury (ALI) is a severe form of respiratory failure characterized by altered lung mechanics and refractory hypoxemia. Globally, the condition presents a serious threat to human health. Morin is a potential active monomer that has beneficial therapeutic effects in ALI; however, its mechanism of action remains unclear. Herein, we found significant elevation of inflammation and pyroptosis in the lung tissue of mice with lipopolysaccharide-induced ALI. Additionally, morin blocked the activation of the TLR4/TRAF6/NF-κB pathway and synergically inhibited the entry of p65 into the nucleus by downregulating the expression of Kruppel-like factor 5. Morin also inhibited caspase-1 activation and protected the GSDMD protein from cleavage. These findings are evidence that morin alleviates ALI by blocking the NF-κB pathway, reducing inflammation, and inhibiting macrophage pyroptosis.

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Immunotherapy strategies and prospects for acute lung injury: Focus on immune cells and cytokines

Cited by 12 publications

References 119 publications

Upregulation of PGC-1α expression by pioglitazone mediates prevention of sepsis-induced acute lung injury

Upregulation of PGC-1α expression by pioglitazone mediates prevention of sepsis-induced acute lung injury

Host PTX3 Protein and Bacterial Capsule Coordinately Regulate the Inflammatory Response during Streptococcus suis Infection

Morin improves LPS-induced acute lung injury by inhibiting pyroptosis and inflammatory response of macrophages

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