ALX/FPR2 receptor for RvD1 is expressed and functional in salivary glands

Nelson, James W.; Leigh, Noel J.; Mellas, Rachel E.; McCall, Andrew D.; Aguirre, Alfredo; Baker, Olga J.

doi:10.1152/ajpcell.00284.2013

Cited by 46 publications

(61 citation statements)

References 47 publications

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“…Besides its expression in immune cells such as macrophages and neutrophils, FPR2/ALX receptors have been found in epithelial cells, endothelial cells, microglia, salivary glands, cornea, spleen, lung and vascular smooth muscle (Bonnans et al, 2007;Chiang et al, 2006;Levy et al, 2002;Migeotte et al, 2006;Nelson et al, 2014;Wilson et al, 2008). In the present report it is shown that FPR2/ALX receptor is constitutively expressed in VSMC and that LPS increased its expression in both the cell line A7r5 and mouse aorta.…”

Section: Discussionsupporting

confidence: 58%

FPR2/ALX activation reverses LPS-induced vascular hyporeactivity in aorta and increases survival in a pneumosepsis model

Horewicz¹,

Crestani²,

Rezende³

et al. 2015

European Journal of Pharmacology

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Section: Discussionsupporting

confidence: 58%

FPR2/ALX activation reverses LPS-induced vascular hyporeactivity in aorta and increases survival in a pneumosepsis model

Horewicz¹,

Crestani²,

Rezende³

et al. 2015

European Journal of Pharmacology

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“…Other authors showed that the formyl peptide receptor 2 (Fpr2), which we found significantly upregulated in our microarrays (Table 1), is expressed in acinar cells of mouse SMG (38). This receptor promotes intracellular calcium responses 8.…”

Section: Discussionmentioning

confidence: 54%

“…and phosphorylation of ERK1/2 and Akt proteins which are associated with cell survival pathways (38). In addition, resolvin D1 (RvD1), which is a short-lived bioactive lipid produced during termination of inflammation and also a ligand for Fpr2, elicits anti-inflammatory and proresolving actions to prevent cell damage and promote tissue repair during the resolution of an inflammatory process (38).…”

Section: Discussionmentioning

confidence: 99%

“…In addition, resolvin D1 (RvD1), which is a short-lived bioactive lipid produced during termination of inflammation and also a ligand for Fpr2, elicits anti-inflammatory and proresolving actions to prevent cell damage and promote tissue repair during the resolution of an inflammatory process (38). The upregulation of Fpr2 in the SMG of PAP Ϫ/Ϫ mice could in part explain the lack of extensive tissue damage in our mice as opposed to the damage observed in mouse models of autoimmune diseases such as Sjögren's syndrome (60).…”

Section: Discussionmentioning

confidence: 99%

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Prostatic acid phosphatase is the main acid phosphatase with 5′-ectonucleotidase activity in the male mouse saliva and regulates salivation

Araujo

Quintero

Kipar

et al. 2014

American Journal of Physiology-Cell Physiology

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Araujo CL, Quintero IB, Kipar A, Herrala AM, Pulkka AE, Saarinen L, Hautaniemi S, Vihko P. Prostatic acid phosphatase is the main acid phosphatase with 5=-ectonucleotidase activity in the male mouse saliva and regulates salivation. Am J Physiol Cell Physiol 306: C1017-C1027, 2014. First published April 9, 2014; doi:10.1152/ajpcell.00062.2014.-We have previously shown that in addition to the well-known secreted isoform of prostatic acid phosphatase (sPAP), a transmembrane isoform exists (TMPAP) that interacts with snapin (a SNARE-associated protein) and regulates the endo-/exocytic pathways. We have also shown that PAP has 5=-ectonucleotidase and thiamine monophosphatase activity and elicits antinociceptive effects in mouse models of chronic inflammatory and neuropathic pain. Therefore, to determine the physiological role of PAP in a typical exocrine organ, we studied the submandibular salivary gland (SMG) of PAP Ϫ/Ϫ and wild-type C57BL/6J mice by microarray analyses, microRNA sequencing, activity tests, immunohistochemistry, and biochemical and physiological analyses of saliva. We show that PAP is the main acid phosphatase in the wild-type male mouse saliva, accounting for 50% of the total acid phosphatase activity, and that it is expressed only in the granular convoluted tubules of the SMGs, where it is the only 5=-ectonucleotidase. The lack of PAP in male PAP Ϫ/Ϫ mice was associated with a significant increase in the salivation volume under secretagogue stimulation, overexpression of genes related to cell proliferation (Mki67, Aurkb, Birc5) and immune response (Irf7, Cxcl9, Ccl3, Fpr2), and upregulation of miR-146a in SMGs. An increased and sustained acinar cell proliferation was detected without signs of glandular hyperplasia. Our results indicate that in PAP Ϫ/Ϫ mice, SMG homeostasis is maintained by an innate immune response. Additionally, we suggest that in male mice, PAP via its 5=-ectonucleotidase activity and production of adenosine can elicit analgesic effects when animals lick their wounds. acid phosphatase; transmembrane prostatic acid phosphatase; 5=-ectonucleotidase activity; TMPase activity; submandibular salivary gland PROSTATIC ACID PHOSPHATASE (PAP, E.C. 3.1.3.2) is a tartratesensitive histidine acid phosphatase enzyme with two known isoforms, the secreted (sPAP) and the type-I transmembrane (TMPAP) isoform, originating from alternative splicing of the same gene (Acpp) (45). Both isoforms are widely expressed in human and mouse tissues. In humans, PAP is predominately expressed in the prostate gland. TMPAP contains an extracellular NH 2 -terminal catalytic domain and a cytosolic COOHterminal domain, carrying a tyrosine-based endosomal/lysosomal targeting motif (Yxx) (45). In addition, TMPAP is an integral membrane protein of cells and is located in the plasma and vesicular membranes, from where it cycles through the endocytic/exocytic pathway via endosomes, multivesicular endosomes, lysosomes, and exosomes (46). Unlike the activity of other acid phosphatases, such as those derived from erythroc...

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“…70 Resolvins also interacted with cytokines by blocking TNF-a-mediated effects in salivary gland tissue. 71 Importantly, the regulation of pro-resolving mediators appear to be influenced by neuronal functioning and may be reduced after neuronal injury and dysfunction associated with a reduction in Netrin-1 affecting resolvin D1 production. 72 Figure 3 (a) Normal nociceptor response to a noxious stimulus is shown.…”

Section: Peripheral Sensitizationmentioning

confidence: 99%

Neuropathic ocular pain: an important yet underevaluated feature of dry eye

Galor

Levitt

Felix

et al. 2014

Eye

182

187

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Dry eye has gained recognition as a public health problem given its prevalence, morbidity, and cost implications. Dry eye can have a variety of symptoms including blurred vision, irritation, and ocular pain. Within dry eyeassociated ocular pain, some patients report transient pain whereas others complain of chronic pain. In this review, we will summarize the evidence that chronicity is more likely to occur in patients with dysfunction in their ocular sensory apparatus (ie, neuropathic ocular pain). Clinical evidence of dysfunction includes the presence of spontaneous dysesthesias, allodynia, hyperalgesia, and corneal nerve morphologic and functional abnormalities. Both peripheral and central sensitizations likely play a role in generating the noted clinical characteristics. We will further discuss how evaluating for neuropathic ocular pain may affect the treatment of dry eye-associated chronic pain.

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ALX/FPR2 receptor for RvD1 is expressed and functional in salivary glands

Abstract: Nelson JW, Leigh NJ, Mellas RE, McCall AD, Aguirre A, Baker OJ. ALX/FPR2 receptor for RvD1 is expressed and functional in salivary glands.

Cited by 46 publications

References 47 publications

FPR2/ALX activation reverses LPS-induced vascular hyporeactivity in aorta and increases survival in a pneumosepsis model

FPR2/ALX activation reverses LPS-induced vascular hyporeactivity in aorta and increases survival in a pneumosepsis model

Prostatic acid phosphatase is the main acid phosphatase with 5′-ectonucleotidase activity in the male mouse saliva and regulates salivation

Neuropathic ocular pain: an important yet underevaluated feature of dry eye

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