PACAP Stimulates the Release of Interleukin‐6 in Cultured Rat Müller Cells

Abstract

We have investigated the in vivo effect of PACAP on rat Müller cells that are the predominant glial element in the retina. Müller cells were treated with PACAP38, either alone or in the presence of the PACAP-selective antagonist, PACAP6-38. Cellular proliferation was determined by measuring the incorporation of bromodeoxyuridine, while interleukin-6 (IL-6) levels in the culture medium were examined using a B9 cell bioassay. In cultured rat Müller cells, the expression of PACAP receptor (PAC1-R) was assessed with immunohistochemistry using a PAC1-R-specific antiserum. PACAP stimulated IL-6 production in Müller cells at a concentration as low as 10(-12) M, which was not sufficient to induce cell proliferation. This elevation of IL-6 production was significantly inhibited by PACAP6-38. These data suggest that Müller cells are one of the target cells for PACAP, stimulating the release of IL-6, and providing a mechanism whereby PACAP exerts a significant neuroprotective effect in the retina.

Functional Identification of Cell Phenotypes Differentiating from Mice Retinal Neurospheres Using Single Cell Calcium Imaging

“…For instance, these cells in culture accumulate cyclic AMP induced by catecholamines (Kubrusly et al 2008), display GABA uptake properties (De Sampaio Schitine et al 2007) and PACAP-induced activation of adenylyl cyclase (Kubrusly et al 2005). They also express glutamic acid decarboxylase, beta 2 nicotine acetylcholine receptors, enzymes of catecholamine metabolism, including tyrosine hydroxylase (Kubrusly et al 2005(Kubrusly et al , 2008Seki et al 2006), glutamate (Ramirez and Lamas 2009), and muscarinic acetylcholine receptors (Wakakura et al 1998). Chick Müller cells in culture express several excitatory amino acids (EAAs) receptors that are coupled to inositol triphosphate mobilization and 45 Ca 2?…”

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

“…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).…”

Involvement of Müller glial cells in epiretinal membrane formation

“…Infiltrating cells, retinal glial cells, and pigment epithelial cells are possible sources of IL-6, IL-1ß, TNFα, and interferon-γ in the vitreous of patients with PVR [18,[195][196][197][198][199][200][201]. Müller cells produce IL-6 [202,203], e.g. upon stimulation with IL-1ß and advanced glycation end products [204,205].…”