Regulation by P2 agonists of the intracellular calcium concentration in epithelial cells freshly isolated from rat trachea

Marino, Aída; Rodrig, Y; Metioui, Mourad; Lagneaux, Laurence; Alzola, Eduardo; Fernández, M; Fogarty, David; Matute, Carlos; Moran, Arie; Dehaye, Jean-Paul

doi:10.1016/s1388-1981(99)00111-0

Cited by 17 publications

(17 citation statements)

References 32 publications

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“…Kim and colleagues (39) previously reported that human nasal epithelial cells express P2X 7 mRNA, but did not show protein expression or pore activity. Our results reinforce those from animal models, where studies indicate airway epithelial cells express P2X 7 mRNA, protein, and channel activity (40)(41)(42). In addition, the ATP-initiated increase in rapid BEC IL-1 cytokine release was augmented by TLR3 engagement.…”

Section: Discussionsupporting

confidence: 88%

Rhinovirus-Induced IL-1β Release from Bronchial Epithelial Cells Is Independent of Functional P2X₇

Shi

Manthei²,

Guadarrama³

et al. 2012

Am J Respir Cell Mol Biol

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Airway epithelial cell defenses to viral infections are often compromised in disease or injury. Danger molecules, including ATP, are released during infection and contribute to nucleotide receptordependent inflammatory responses, largely through P2X 7 . Although respiratory epithelium has been shown to express a variety of nucleotide receptors, the functional contribution of P2X 7 to the epithelial cell inflammatory response is unclear. We used human donor bronchial epithelial cells (BECs) and primary brushed epithelium to explore responses upon nucleotide and Toll-like receptor stimulation. P2X 7 messenger RNA and protein were observed in unprimed BECs, whereas inflammatory cytokine stimulation increased both messenger RNA and protein. Functional pore activity characteristic of P2X 7 was observed in BECs, and IL-1b was rapidly released by BECs after Toll-like receptor 3 agonist, polyinosinepolycytidylic acid, priming followed by ATP administration, although no change was observed in IL-18 release. BECs produced more IL-1b after stimulation with polyinosine-polycytidylic acid than LPS, showing a different preferential response than monocytes. In addition, blockade of nucleotide receptors with oxidized ATP significantly increased human rhinovirus (HRV) recovered 24 hours after infection in BECs, whereas 29-39-O-(4-benzoylbenzoyl) ATP treatment of brushed epithelial cells and respiratory cell lines nonsignificantly decreased HRV recovery. IL-1b release was detected after HRV infection in both BECs and brushed cells, but BzATP did not significantly increase IL-1b release further. BEC processing of pro-IL-1b to the mature, cleaved, 17-kD form was confirmed by Western blotting. These results support the expression of functional P2X 7 in human lung epithelium, although its role in epithelial pathogen defense is likely independent of IL-1 family cytokine processing.Keywords: P2X 7 ; IL-1b; human rhinovirus; respiratory epithelium; danger signalingRespiratory epithelium provides a complex physical barrier against foreign material, and is the first site of exposure to pathogens. When infected, respiratory epithelium may serve as a primary site of replication. Once a cell detects an invasion, it may attempt to destroy the pathogen or signal for help to prevent other cells from succumbing to its fate (1). Airway epithelial cells are sources of inflammatory cytokines, including IL-1b and IL-18, as detailed in previously published reviews (2-4), and sometimes generated by unclear mechanisms upon exposure to cigarette smoke (5) or other injury models, including bleomycin (6). Epithelium also responds to a host of other cytokines, including TNF-a and IFN-g, present during both viral and gram-negative bacterial infections. Efficient release of the IL-1 family of cytokines involves synthesis induced by ligand activation of Toll-like receptors (TLRs) and P2X 7 -regulated activation of caspase 1, leading to proteolytic cleavage (7). Previous studies in rodent epithelial cells document messenger RNA (mRNA) and protein expression of...

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Section: Discussionsupporting

confidence: 88%

Rhinovirus-Induced IL-1β Release from Bronchial Epithelial Cells Is Independent of Functional P2X₇

Shi

Manthei²,

Guadarrama³

et al. 2012

Am J Respir Cell Mol Biol

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“…RT-PCR and pharmacological studies identified P2Y 1 , P2Y 2 , P2X4, and P2X7 receptors that regulate the increase in [Ca 2ϩ ] i in freshly isolated rat tracheal epithelial cells (Marino et al, 1999). The P2X receptors on rabbit tracheal ciliated cells were also identified as P2X4 and P2X7 subtypes (Ma et al, 2006).…”

Section: A Epithelial Cellsmentioning

confidence: 97%

Purinergic Signaling in the Airways

Burnstock

Brouns²,

Adriaensen³

et al. 2012

Pharmacol Rev

173

158

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“…These are seen in freshly isolated tissue from rabbit airway (254,297) as well as several other epithelial cell lines (453). In the case of the airways, considerable evidence implicates the P2X 7 subunit.…”

Section: Airway Epitheliummentioning

confidence: 99%

“…In the case of the airways, considerable evidence implicates the P2X 7 subunit. The membrane currents are nondesensitizing and develop faster onset kinetics with repeated application (254), BzATP is more potent than ATP at causing a sustained increase in [Ca 2ϩ ] i (297), and extracellular sodium strongly inhibits the ATP response (293). Ciliary beat frequency increases as a result of calcium entry through the P2X receptor, and this effect is much enhanced at low extracellular sodium concentrations (293).…”

Section: Airway Epitheliummentioning

confidence: 99%

Molecular Physiology of P2X Receptors

North

2002

Physiological Reviews

2,678

128

3,397

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P2X receptors are membrane ion channels that open in response to the binding of extracellular ATP. Seven genes in vertebrates encode P2X receptor subunits, which are 40–50% identical in amino acid sequence. Each subunit has two transmembrane domains, separated by an extracellular domain (∼280 amino acids). Channels form as multimers of several subunits. Homomeric P2X1, P2X2, P2X3, P2X4, P2X5, and P2X7 channels and heteromeric P2X2/3 and P2X1/5 channels have been most fully characterized following heterologous expression. Some agonists (e.g., αβ-methylene ATP) and antagonists [e.g., 2′,3′- O-(2,4,6-trinitrophenyl)-ATP] are strongly selective for receptors containing P2X1 and P2X3subunits. All P2X receptors are permeable to small monovalent cations; some have significant calcium or anion permeability. In many cells, activation of homomeric P2X7 receptors induces a permeability increase to larger organic cations including some fluorescent dyes and also signals to the cytoskeleton; these changes probably involve additional interacting proteins. P2X receptors are abundantly distributed, and functional responses are seen in neurons, glia, epithelia, endothelia, bone, muscle, and hemopoietic tissues. The molecular composition of native receptors is becoming understood, and some cells express more than one type of P2X receptor. On smooth muscles, P2X receptors respond to ATP released from sympathetic motor nerves (e.g., in ejaculation). On sensory nerves, they are involved in the initiation of afferent signals in several viscera (e.g., bladder, intestine) and play a key role in sensing tissue-damaging and inflammatory stimuli. Paracrine roles for ATP signaling through P2X receptors are likely in neurohypophysis, ducted glands, airway epithelia, kidney, bone, and hemopoietic tissues. In the last case, P2X7 receptor activation stimulates cytokine release by engaging intracellular signaling pathways.

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Regulation by P2 agonists of the intracellular calcium concentration in epithelial cells freshly isolated from rat trachea

Cited by 17 publications

References 32 publications

Rhinovirus-Induced IL-1β Release from Bronchial Epithelial Cells Is Independent of Functional P2X₇

Rhinovirus-Induced IL-1β Release from Bronchial Epithelial Cells Is Independent of Functional P2X₇

Purinergic Signaling in the Airways

Molecular Physiology of P2X Receptors

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Regulation by P2 agonists of the intracellular calcium concentration in epithelial cells freshly isolated from rat trachea

Cited by 17 publications

References 32 publications

Rhinovirus-Induced IL-1β Release from Bronchial Epithelial Cells Is Independent of Functional P2X7

Rhinovirus-Induced IL-1β Release from Bronchial Epithelial Cells Is Independent of Functional P2X7

Purinergic Signaling in the Airways

Molecular Physiology of P2X Receptors

Contact Info

Product

Resources

About

Rhinovirus-Induced IL-1β Release from Bronchial Epithelial Cells Is Independent of Functional P2X₇

Rhinovirus-Induced IL-1β Release from Bronchial Epithelial Cells Is Independent of Functional P2X₇