Hemokinin-1 is an important mediator of endotoxin-induced acute airway inflammation in the mouse

Hajna, Zsófia; Borbély, Éva; Kemény, Ágnes; Botz, Bálint; Kereskai, László; Szolcsányi, Janós; Pintér, Erika; Paige, Christopher J.; Berger, Alexandra; Helyes, Zsuzsanna

doi:10.1016/j.peptides.2014.12.002

Cited by 9 publications

(6 citation statements)

References 42 publications

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“…30,31,32,33 Furthermore, an intranasal administration of an E. coli endotoxin, lipopolysaccharide (LPS), induces airway inflammation. 34,35,36 We, therefore, investigated whether intranasal administration of a heat-inactivated lab strain of E. coli , DH5-α, could induce the formation of BALT.…”

Section: Resultsmentioning

confidence: 99%

Application of light sheet microscopy for qualitative and quantitative analysis of bronchus-associated lymphoid tissue in mice

Mzinza

Fleige

Laarmann³

et al. 2018

Cell Mol Immunol

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Bronchus-associated lymphoid tissue (BALT) develops at unpredictable locations around lung bronchi following pulmonary inflammation. The formation and composition of BALT have primarily been investigated by immunohistology that, due to the size of the invested organ, is usually restricted to a limited number of histological sections. To assess the entire BALT of the lung, other approaches are urgently needed. Here, we introduce a novel light sheet microscopy-based approach for assessing lymphoid tissue in the lung. Using antibody staining of whole lung lobes and optical clearing by organic solvents, we present a method that allows in-depth visualization of the entire bronchial tree, the lymphatic vasculature and the immune cell composition of the induced BALT. Furthermore, three-dimensional analysis of the entire lung allows the qualitative and quantitative enumeration of the induced BALT. Using this approach, we show that a single intranasal application of the replication-deficient poxvirus MVA induces BALT that constitutes up to 8% of the entire lung volume in mice deficient in CCR7, in contrast to wild type mice (WT). Furthermore, BALT induced by heat-inactivated E. coli is dominated by a pronounced T cell infiltration in Cxcr5-deficient mice, in contrast to WT mice.

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Section: Resultsmentioning

confidence: 99%

Application of light sheet microscopy for qualitative and quantitative analysis of bronchus-associated lymphoid tissue in mice

Mzinza

Fleige

Laarmann³

et al. 2018

Cell Mol Immunol

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“…HK-1 can elicit pain when injected intrathecally [34,43], and Tac4 -/mice have reduced nocifensive behavior in chemically-induced pain and suppressed hyperalgesia/allodynia in chronic inflammatory and neuropathic pain models [41,102]. In inflammatory pain and arthritis, a pro-inflammatory component is also likely to contribute to its action, since HK-1 expression was described in the immune system as well [30,33,103] and Tac4 deficiency also alleviated experimental lung inflammation [42]. On the other hand, HK-1 was shown to have a direct role in central nociceptive sensitization, as spinal microglia and astrocyte activation was also attenuated in Tac4 -/mice after nerve injury [41].…”

Section: Discussionmentioning

confidence: 99%

“…Although a few studies reported antibody development (e.g., [38]) or a recent immunohistochemical study on the TG with an in-house developed antibody [39], there are still no commercially available antibodies against HK-1. Despite the structural similarities and common receptors of HK-1 and SP, some of their functions appear to be different, even opposing each other [36,[40][41][42][43]. This could be explained by different binding sites and different signalling pathways by HK-1 compared to SP even at the NK-1 receptor, but a specific target is suggested to mediate several actions of HK-1 [36].…”

Section: Introductionmentioning

confidence: 98%

Hemokinin-1 Gene Expression Is Upregulated in Trigeminal Ganglia in an Inflammatory Orofacial Pain Model: Potential Role in Peripheral Sensitization

Aczél

Kecskés

Kun

et al. 2020

IJMS

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A large percentage of primary sensory neurons in the trigeminal ganglia (TG) contain neuropeptides such as tachykinins or calcitonin gene-related peptide. Neuropeptides released from the central terminals of primary afferents sensitize the secondary nociceptive neurons in the trigeminal nucleus caudalis (TNC), but also activate glial cells contributing to neuroinflammation and consequent sensitization in chronic orofacial pain and migraine. In the present study, we investigated the newest member of the tachykinin family, hemokinin-1 (HK-1) encoded by the Tac4 gene in the trigeminal system. HK-1 had been shown to participate in inflammation and hyperalgesia in various models, but its role has not been investigated in orofacial pain or headache. In the complete Freund’s adjuvant (CFA)-induced inflammatory orofacial pain model, we showed that Tac4 expression increased in the TG in response to inflammation. Duration-dependent Tac4 upregulation was associated with the extent of the facial allodynia. Tac4 was detected in both TG neurons and satellite glial cells (SGC) by the ultrasensitive RNAscope in situ hybridization. We also compared gene expression changes of selected neuronal and glial sensitization and neuroinflammation markers between wild-type and Tac4-deficient (Tac4-/-) mice. Expression of the SGC/astrocyte marker in the TG and TNC was significantly lower in intact and saline/CFA-treated Tac4-/- mice. The procedural stress-related increase of the SGC/astrocyte marker was also strongly attenuated in Tac4-/- mice. Analysis of TG samples with a mouse neuroinflammation panel of 770 genes revealed that regulation of microglia and cytotoxic cell-related genes were significantly different in saline-treated Tac4-/- mice compared to their wild-types. It is concluded that HK-1 may participate in neuron-glia interactions both under physiological and inflammatory conditions and mediate pain in the trigeminal system.

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“…In the endotoxin-induced acute pneumonitis model, breathing frequency (f) and carbachol-induced airway reactivity were measured before and 24 h after intranasal PBS/LPS administration [95]. Bronchoconstriction was induced by increasing concentrations (5.5, 11 and 22 mM) of the muscarinic receptor agonist carbachol (50 µL/mouse), and the Penh (enhanced pause) value was determined.…”

Section: Investigation Of Airway Function and Bronchial Responsivenessmentioning

confidence: 99%

Complex Regulatory Role of the TRPA1 Receptor in Acute and Chronic Airway Inflammation Mouse Models

Hajna

Csekő

Kemény

et al. 2020

IJMS

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The Transient Receptor Potential Ankyrin 1 (TRPA1) cation channel expressed on capsaicin-sensitive afferents, immune and endothelial cells is activated by inflammatory mediators and exogenous irritants, e.g., endotoxins, nicotine, crotonaldehyde and acrolein. We investigated its involvement in acute and chronic pulmonary inflammation using Trpa1 gene-deleted (Trpa1−/−) mice. Acute pneumonitis was evoked by intranasal Escherichia coli endotoxin (lipopolysaccharide: LPS) administration, chronic bronchitis by daily cigarette smoke exposure (CSE) for 4 months. Frequency, peak inspiratory/expiratory flows, minute ventilation determined by unrestrained whole-body plethysmography were significantly greater, while tidal volume, inspiratory/expiratory/relaxation times were smaller in Trpa1−/− mice. LPS-induced bronchial hyperreactivity, myeloperoxidase activity, frequency-decrease were significantly greater in Trpa1−/− mice. CSE significantly decreased tidal volume, minute ventilation, peak inspiratory/expiratory flows in wildtypes, but not in Trpa1−/− mice. CSE remarkably increased the mean linear intercept (histopathology), as an emphysema indicator after 2 months in wildtypes, but only after 4 months in Trpa1−/− mice. Semiquantitative histopathological scores were not different between strains in either models. TRPA1 has a complex role in basal airway function regulation and inflammatory mechanisms. It protects against LPS-induced acute pneumonitis and hyperresponsiveness, but is required for CSE-evoked emphysema and respiratory deterioration. Further research is needed to determine TRPA1 as a potential pharmacological target in the lung.

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Hemokinin-1 is an important mediator of endotoxin-induced acute airway inflammation in the mouse

Cited by 9 publications

References 42 publications

Application of light sheet microscopy for qualitative and quantitative analysis of bronchus-associated lymphoid tissue in mice

Application of light sheet microscopy for qualitative and quantitative analysis of bronchus-associated lymphoid tissue in mice

Hemokinin-1 Gene Expression Is Upregulated in Trigeminal Ganglia in an Inflammatory Orofacial Pain Model: Potential Role in Peripheral Sensitization

Complex Regulatory Role of the TRPA1 Receptor in Acute and Chronic Airway Inflammation Mouse Models

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