Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) Is a Regulator of Astrocytes: PACAP Stimulates Proliferation and Production of Interleukin 6 (IL-6), but not Nerve Growth Factor (NGF), in Cultured Rat Astrocyte

Tatsuno, Ichiro; Morio, Hiroshi; Tanaka, Tomoaki; Uchida, Daigaku; Hirai, Aizan; Tamura, Yasushi; Saitō, Yasushi

doi:10.1111/j.1749-6632.1996.tb17508.x

Cited by 45 publications

(20 citation statements)

References 22 publications

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“…Several lines of evidence have suggested that PACAP stimulates the production of interleukin-6 (IL-6), a proinflammatory cytokine, in rat astrocytes and muller cells as well as mouse calvarial osteoblasts (Tatsuno et al, 1996;Seki et al, 2006). IL-6 produced by osteoblasts/stromal cells has been demonstrated as a key factor for excessive bone resorption in physiological conditions such as postmenopausal osteoporosis (Suda et al, 1991;Pfeilschifter et al, 2002;, hyperparathyroidism (Grey et al, 1999) and Paget's disease (Roodman, 2001).…”

Section: Journal Of Cellular Physiologymentioning

confidence: 99%

cAMP activation by PACAP/VIP stimulates IL‐6 release and inhibits osteoblastic differentiation through VPAC2 receptor in osteoblastic MC3T3 cells

Nagata

Tanaka

Minezawa

et al. 2009

Journal Cellular Physiology

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The neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP), a member of the glucagon/vasoactive intestinal peptide (VIP) superfamily, stimulates cyclic AMP accumulation initiating a variety of biological processes such as: neurotropic actions, immune and pituitary function, learning and memory, catecholamine biosynthesis and regulation of cardiopulmonary function. Both osteoclasts and osteoblasts have been shown to express receptors for PACAP/VIP implicated in their role in bone metabolism. To further understand the role of PACAP/VIP family in controlling bone metabolism, we investigated differentiation model of MC3T3-E1 cells, an osteoblastic cell line derived from mouse calvaria. Quantitative RT-PCR analysis demonstrated that MC3T3-E1 cells expressed only VPAC2 receptor and its expression was upregulated during osteoblastic differentiation, whereas VPAC1 and PAC1 receptors were not expressed. Consistent with expression of receptor subtype, both PACAP and VIP stimulate cAMP accumulation in a time- and dose-dependent manner with the similar potency in undifferentiated and differentiated cells, while Maxadilan, a specific agonist for PAC1-R, did not. Furthermore, downregulation of VPAC2-R by siRNA completely blocked cAMP response mediated by PACAP and VIP. Importantly, PACAP/VIP as well as forskolin markedly suppressed the induction of alkaline phosphatase mRNA upon differentiation and the pretreatment with 2',5'-dideoxyadenosine, a cAMP inhibitor, restored its inhibitory effect of PACAP. We also found that PACAP and VIP stimulated IL-6 release, a stimulator of bone resorption, and VPAC2-R silencing inhibited IL-6 production. Thus, PACAP/VIP can activate adenylate cyclase response and regulate IL-6 release through VPAC2 receptor with profound functional consequences for the inhibition of osteoblastic differentiation in MC3T3-E1 cells.

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Section: Journal Of Cellular Physiologymentioning

confidence: 99%

cAMP activation by PACAP/VIP stimulates IL‐6 release and inhibits osteoblastic differentiation through VPAC2 receptor in osteoblastic MC3T3 cells

Nagata

Tanaka

Minezawa

et al. 2009

Journal Cellular Physiology

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“…These studies support the present findings which demonstrate that scratch injury in astrocytic monolayers induces reactive astrocytes and that PAC1-R is a novel marker for these cells. A number of growth factors and cytokines are also released from reactive astrocytes (Ridet et al 1997), and it has been reported that PACAP administration induces the expression of neuroprotective proteins, such as ADNF and ADNP (Dejda et al 2005;Nakamachi et al 2006;Nakamachi et al 2008) and cytokines (Gottschall et al 1994;Tatsuno et al 1996). Such PACAP-inducible factors could be additional candidates as markers of astrocytic activation.…”

Section: Discussionmentioning

confidence: 99%

“…PACAP has a pleiotropic function in the CNS, as a neuroprotectant, neurite outgrowth factor, and inducer of neural stem cell differentiation into astrocytes (Nakamachi et al 2010;Ohno et al 2005;Ohtaki et al 2006Ohtaki et al , 2008Shioda et al 2006;Somogyvari-Vigh and Reglodi 2004;Tamas et al 2006;Watanabe et al 2006a, b). PACAP has also been widely reported to act as a regulator of astrocytes in vitro (Gottschall et al 1994;Tatsuno and Arimura 1994;Tatsuno et al 1990Tatsuno et al , 1996. We have previously reported that immunoreactivity for the PACAP receptor, PAC1-receptor (PAC1-R), is observed in reactive astrocytes following a stub wound brain injury in vivo (Suzuki et al 2003).…”

Section: Introductionmentioning

confidence: 99%

Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) Stimulates Proliferation of Reactive Astrocytes In Vitro

et al. 2010

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Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide originally isolated from ovine hypothalamus. Recently, we have shown that the PACAP receptor (PAC1-R) is expressed in reactive astrocytes following an in vivo stub wound brain injury. However, the functional role of PACAP has not yet been clarified. In order to investigate the effect of PACAP on the proliferation of reactive astrocytes, a scratch wound paradigm was applied to astrocytic monolayers. Following injury, there was an increase in PAC1-R and glial fibrillary acidic protein (GFAP) immunoreactivity in the astrocytes surrounding the scratch line. PACAP at concentrations of 10(-15) to 10(-7) M was applied immediately after scratching, and the proliferating astrocytes were visualized by multiple immunofluorescence labeling. The percentage of cells that colabeled for Ki67 (a marker of proliferating cells) and GFAP increased in the 10(-11)- and 10(-13)-M PACAP-treated groups. The proliferating astrocytes induced by PACAP treatment mainly occurred in the proximal wound area where many reactive astrocytes were observed. Pretreatment with the PACAP receptor antagonist PACAP6-38 significantly suppressed the PACAP-induced effects. These results strongly suggest that PACAP plays an important role in the proliferation of reactive astrocytes following nerve injury.

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“…These phenomena improved with the administration of PACAP, suggesting that PACAP protects nerve cells through the inhibition of cytochrome c release from the mitochondria [37] (Figure 2). PACAP has also been shown to promote the secretion of interleukin 6 (IL-6) from astrocytes and Muller cells [33,54]. IL-6, an inflammatory cytokine, exerts a neuroprotective effect in the central nervous system [27].…”

Section: Functional Analysis Of Pacap Using Gene-deficient Micementioning

confidence: 99%

PACAP as a neuroprotective factor in ischemic neuronal injuries

Shioda

Nakamachi

2015

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Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) Is a Regulator of Astrocytes: PACAP Stimulates Proliferation and Production of Interleukin 6 (IL-6), but not Nerve Growth Factor (NGF), in Cultured Rat Astrocyte

Cited by 45 publications

References 22 publications

cAMP activation by PACAP/VIP stimulates IL‐6 release and inhibits osteoblastic differentiation through VPAC2 receptor in osteoblastic MC3T3 cells

cAMP activation by PACAP/VIP stimulates IL‐6 release and inhibits osteoblastic differentiation through VPAC2 receptor in osteoblastic MC3T3 cells

Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) Stimulates Proliferation of Reactive Astrocytes In Vitro

PACAP as a neuroprotective factor in ischemic neuronal injuries

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