ライフサイエンスコーパス: pIgR

1 pIgR actively transports dIgA from the circulation acros

2 pIgR down-regulation in COPD correlates with disease sev

3 pIgR downregulation was selectively observed in patients

4 pIgR expression is reduced in chronic obstructive pulmon

5 pIgR expression is, in part, driven by aberrant STAT6 pa

6 pIgR expression was decreased in the ethmoidal mucosa in

7 pIgR immunostaining in the bronchial epithelium is decre

8 pIgR mRNA and protein also decline in P(+) E. coli-infec

9 pIgR(-/-) and pIgR(+/+) mice had comparable levels of in

10 IL-4, pIgR, IgA, and phosphorylated JAK-1 were significantly i

11 is-selected peptides map to the same 402-410 pIgR-binding Calpha3 site.

12 of receptor oligomerization, we show that a pIgR:zeta chimeric receptor expressed in Jurkat cells in

13 We propose that it may be possible to use a pIgR binding motif to deliver antigen-specific dIgA and

14 de detailed models for SC structure, address pIgR evolution, and demonstrate that SC uses multiple co

15 All pIgR binding IgA sequences contain a conserved three ami

16 We now report that levels of IRF-1 and pIgR mRNA are coordinately regulated in HT-29 cells by T

17 acterial numbers significantly in normal and pIgR-deficient mice, and depletion of IgG abrogated this

18 pIgR(-/-) and pIgR(+/+) mice had comparable levels of inflammation, de

19 ysaccharide Ab locally and systemically, and pIgR(-/-) mice produced levels of total serum Ab after v

20 omes and subsequently intersects the TfR and pIgR pathways at a perinuclear Rab11-negative compartmen

21 ction, because both vaccinated wild-type and pIgR(-/-) mice were fully protected from lethal systemic

22 he Th2 cytokines, IL-4 and IL-13, as well as pIgR, and luminal IgA compared with chow.

23 to both solubilized and membrane-associated pIgR, suggesting that binding can occur while the pIgR i

24 further investigated the interaction between pIgR and CaM using Madin-Darby canine kidney cells stabl

25 nd of the resulting immune complexes to bind pIgR.

26 fork' structure that is involved in binding pIgR.

27 ion of pIgR transcytosis and/or signaling by pIgR.

28 ess IgA dependent in mice, was unaffected by pIgR deficiency, indicating that pIgR had no physiologic

29 Inasmuch as this mouse B cell pIgR binds IgM better than IgA, it is similar to human p

30 y identical with that of the epithelial cell pIgR throughout its external, transmembrane, and intracy

31 from rat, mouse, and rabbit epithelial cell pIgRs that bind IgA but not IgM.

32 In contrast, pIgR transcription was up-regulated in smokers with or w

33 In contrast, pIgR(-/-) mice, which lack the receptor to transcytose p

34 In ALI (vs. submerged) cultures, pIgR expression was strongly induced, whereas pIgR expre

35 It is proposed that P fimbriae decrease pIgR expression in the kidney and consequently decrease

36 Polymeric IgR-deficient (pIgR(-/-)) mice, which lack the receptor that transports

37 polymeric immunoglobulin receptor-deficient (pIgR(-/-)) mice, which lack SIgA, spontaneously develop

38 ich in turn stimulates the transport of dIgA-pIgR complex from a postmicrotubule compartment to the a

39 P(+)-infected mice downregulate pIgR mRNA and protein levels compared with P(-)-infected

40 structure of teleost fish SC (tSC), an early pIgR ancestor.

41 This enables pIgR molecules that have bound dIgA at the basolateral s

42 up-regulate transcription of genes encoding pIgR and a number of proinflammatory factors, but the ef

43 Expression of mRNA encoding pIgR and several proinflammatory genes increased acutely

44 Epithelial pIgR expression is decreased in patients with CRSwNP and

45 ine whether P(+) E. coli regulate epithelial pIgR expression and IgA transport into the urine.

46 African green monkey kidney cells expressing pIgR demonstrated HIV excretion that was dependent on th

47 Darby Canine Kidney transcytosis assay, for pIgR-mediated transport through epithelial cells.

48 patients retains its aberrant imprinting for pIgR expression.

49 Selection of random peptides for pIgR binding and comparison with the IgA sequence sugges

50 e lacking the J chain, which is required for pIgR-dependent transepithelial IgA transport.

51 eries of patients (n = 116) were studied for pIgR expression and regulation.

52 Furthermore, pIgR is the most prominent 35S-labeled CaM-binding prote

53 However, pIgR(-/-) mice had approximately 5-fold more systemic Ig

54 A missense mutation in human pIgR, A580V, is associated with IgA nephropathy and naso

55 Deletional analysis of human pIgR revealed that the lack of either D3 or D4 resulted

56 inding motif(s) in the D3/D4 region of human pIgR, which is functionally separated from the IgA-bindi

57 We report here that the human pIgR (hpIgR) can bind to a major pneumococcal adhesin, C

58 IgM better than IgA, it is similar to human pIgR and differs from rat, mouse, and rabbit epithelial

59 sting of 16HBEo cells transfected with human pIgR complementary DNA, which overexpress the receptor,

60 such as transferrin (TfR) and polymeric IgA (pIgR) receptors.

61 The polymeric IgR (pIgR) mediates transcytosis of IgA across epithelial bar

62 a dominant role, was severely compromised in pIgR-deficient mice despite significant fecal IgA output

63 The decrease in pIgR was associated with decreased urinary IgA levels in

64 We propose that the defects in pIgR trafficking caused by the A580V mutation may underl

65 ive airway wall remodelling and emphysema in pIgR(-/-) mice are associated with an altered lung micro

66 IV replication, nor did D47A and D19A IgA in pIgR- cells, incapable of transcytosing IgA.

67 exposure to TNF caused a marked increase in pIgR mRNA stability and a small but significant decrease

68 this recruitment was a striking induction in pIgR expression by the bronchial epithelium and a subseq

69 Several factors increase pIgR expression in human epithelial cells, including IL-

70 epithelial HT-29 cells with IL-17 increased pIgR expression.

71 inflammation were associated with increased pIgR and PAFr levels in the lungs and increased suscepti

72 a crucial role for this cytokine in inducing pIgR expression by the epithelium.

73 ogenous TGF-beta1 dose-dependently inhibited pIgR production, whereas pIgR increased on blockade of T

74 fic for a commensal Ag, increased intestinal pIgR and IgA.

75 The levels of intestinal pIgR and IgA in B6.IL-17R (IL-17R(-/-)) mice were lower

76 estinal homeostasis by regulating intestinal pIgR expression and IgA secretion.

77 Kidney pIgR and urine IgA levels were analyzed in a mouse model

78 been examined using polymeric IgR knockout (pIgR(-/-)) mice, which lack the ability to actively secr

79 ton X-114-solubilized, metabolically labeled pIgR-expressing Madin-Darby canine kidney cells.

80 basolateral membrane from CRE, Megalin, like pIgR, traffics to subapical Rab11-positive apical recycl

81 This study also links pIgR down-regulation to TGF-beta-driven reprogramming of

82 d from the published sequence of mouse liver pIgR indicate that T560 cells express mRNA virtually ide

83 required for their transport into the lumen, pIgR or J chain, cleared C. rodentium normally.

84 TNF production was insufficient to maintain pIgR and proinflammatory gene expression after withdrawa

85 s also demonstrated that avian and mammalian pIgR share related, but distinct, mechanisms of ligand b

86 Although several mammalian pIgR cDNAs, including mouse, have been cloned, genomic s

87 gA that increased caspase activation in MDCK-pIgR+ cells compared to serum-derived IgA from controls

88 t or fixed in 4% paraformaldehyde to measure pIgR expression via immunohistochemistry.

89 Tissue was homogenized to measure pIgR expression via Western blot or fixed in 4% paraform

90 immunoblots with specific rabbit anti-mouse pIgR.

91 In summary, we have isolated the murine pIgR gene and described its structure and organization.

92 isolation and characterization of the murine pIgR gene that spans 32 kb and contains 11 exons.

93 tably expressing cloned wild-type and mutant pIgR.

94 Wild-type, but not pIgR(-/-) mice were protected against infection with ser

95 ot the Tyr734), controls both the ability of pIgR to cause dIgA-induced tyrosine phosphorylation of t

96 t the basolateral surface and the ability of pIgR to dimerize.

97 rs or deletion of the last 30 amino acids of pIgR cytoplasmic tail prevents IgA-stimulated protein ty

98 Analysis of pIgR deletion mutants reveals that the same discrete por

99 Furthermore, CbpA binding of pIgR did not appear to require Ca2+ or Mg2+.

100 Re-derivation of pIgR(-/-) mice in germ-free conditions or treatment with

101 gnaling, Arg657 in the cytoplasmic domain of pIgR, and possibly GTP hydrolysis by rab3b.

102 tly interacts with the cytoplasmic domain of pIgR.

103 e, we demonstrate that in vivo expression of pIgR mRNA is greatly depressed in the intestine and live

104 ation moves across the cell independently of pIgR movement or microtubules and acts through the tyros

105 Our data suggest that inhibition of pIgR and PECAM-1 has the potential to prevent pneumococc

106 Individual mice with lower levels of pIgR and intestinal-secreted IgA correlated with increas

107 g pneumonia, aged mice had reduced levels of pIgR and PAFr and less NFkB activation, despite greater

108 ecrosis factor-alpha had increased levels of pIgR and PAFr in their lungs and were more susceptible t

109 Both dsRNA and LPS up-regulated levels of pIgR mRNA and cell surface pIgR protein.

110 nd IFN-gamma increase steady state levels of pIgR mRNA in both human intestinal (HT29) and airway (Ca

111 ependent increases in steady state levels of pIgR mRNA were inhibited by cycloheximide and by protein

112 IRF-1 only weakly correlated with levels of pIgR mRNA, suggesting that additional transcription fact

113 The extra-cellular portion of pIgR consists of five Ig-like domains (D1-D5), each of w

114 of pIgR and pIgA, and seemingly the rate of pIgR cleavage.

115 obulin receptor [pIgR]), apical recycling of pIgR-IgA, and accumulation of newly synthesized GP-135 a

116 This region of pIgR constitutes an autonomous basolateral targeting sig

117 st that CaM may be involved in regulation of pIgR transcytosis and/or signaling by pIgR.

118 Through the generation of a series of pIgR chimeric constructs, we have tested the ability of

119 ne IgA was greatly increased in the serum of pIgR-deficient mice, conferred passive protection agains

120 Synthesis of pIgR is up-regulated by the proinflammatory cytokines TN

121 hrough NF-kappaB to enhance transcription of pIgR mRNA.

122 g receptor (pIgR) stimulates transcytosis of pIgR across epithelial cells.

123 mutation reduces the rate of transcytosis of pIgR and pIgA, and seemingly the rate of pIgR cleavage.

124 with thapsigargin stimulates transcytosis of pIgR, while the intracellular Ca chelator BAPTA-AM inhib

125 d to achieve dIgA-stimulated transcytosis of pIgR.

126 These results, together with prior data on pIgR-mediated immune neutralization of luminal cholera t

127 ought to determine the CbpA-binding motif on pIgR by deletional analysis.

128 tein PspC binds, but to a lower extent, only pIgR.

129 to pIgR stimulates transcytosis of the pIgA-pIgR complex via a signal transduction pathway that is d

130 e against respiratory pathogens by promoting pIgR-mediated transport of secretory IgA and IgM into th

131 In contrast, rabbit pIgR (rpIgR) did not bind to CbpA and its expression in

132 he mouse polymeric immuno-globulin receptor (pIgR) is 654 nt long and, despite being surrounded by la

133 found that intestinal polymeric Ig receptor (pIgR) and IgA production was impaired in T cell-deficien

134 fected with the human polymeric Ig receptor (pIgR) and the cells studied by flow cytometric analysis

135 Polymeric Ig receptor (pIgR) is a central player in mucosal immunity that media

136 The polymeric Ig receptor (pIgR) is conserved in mammals and has an avian homologue

137 cates that the receptor is poly-Ig receptor (pIgR) known in humans and domestic cattle to bind both I

138 The polymeric Ig receptor (pIgR) mediates transport of IgA across mucosal epithelia

139 globulin (Ig)A to the polymeric Ig receptor (pIgR) stimulates transcytosis of pIgR across epithelial

140 The polymeric Ig receptor (pIgR) transcytoses its ligand, dimeric IgA (dIgA), from

141 The polymeric Ig receptor (pIgR) transports polymeric Abs across epithelia to the m

142 s, IgA, secreted IgM, polymeric Ig receptor (pIgR), or J chain.

143 The polymeric Ig receptor (pIgR), produced by renal epithelia, transports IgA into

144 fected to express the polymeric Ig receptor (pIgR), were transfected with HIV proviral DNA, and intra

145 ia is mediated by the polymeric Ig receptor (pIgR), which is expressed on the basolateral surface of

146 he apical surface via polymeric Ig receptor (pIgR)-mediated binding and the internalization of HIV-Ig

147 s the hypothesis that polymeric Ig receptor (pIgR)-mediated secretory IgA immunity could be impaired

148 d in the transcytotic polymeric Ig receptor (pIgR).

149 eric Igs (pIg) by the polymeric Ig receptor (pIgR).

150 nal secretions by the polymeric Ig receptor (pIgR).

151 ns is mediated by the polymeric Ig receptor (pIgR).

152 the human polymeric immunoglobulin receptor (pIgR) and enhances pneumococcal adhesion to and invasion

153 ining the polymeric immunoglobulin receptor (pIgR) and located subjacent to the apical surface.

154 eceptors: polymeric immunoglobulin receptor (pIgR) and platelet endothelial cell adhesion molecule (P

155 proteins polymeric immunoglobulin receptor (pIgR) and platelet-activating factor receptor (PAFr) to

156 ing human polymeric immunoglobulin receptor (pIgR) expressing Madine-Darby canine kidney (MDCK) cells

157 that the polymeric immunoglobulin receptor (pIgR) is highly expressed by renal cyst-lining cells.

158 The polymeric immunoglobulin receptor (pIgR) is important in host defense, transporting antibod

159 is of the polymeric immunoglobulin receptor (pIgR) is stimulated by binding of its ligand, dimeric Ig

160 ed by the polymeric immunoglobulin receptor (pIgR) on mucosal and glandular epithelial cells.

161 The polymeric immunoglobulin receptor (pIgR) plays a crucial role in mucosal immunity against m

162 The polymeric immunoglobulin receptor (pIgR) transcytoses dimeric IgA (dIgA) from the basolater

163 ense, the polymeric immunoglobulin receptor (pIgR) transports polymeric IgA and IgM across epithelia

164 tein, the polymeric immunoglobulin receptor (pIgR), and a secretory protein, gp80, we show that pIgR

165 ct of the polymeric immunoglobulin receptor (pIgR), is added during the transit of dimeric IgA throug

166 protein, polymeric immunoglobulin receptor (pIgR), which is reduced during PN.

167 reported polymeric immunoglobulin receptor (pIgR)-binding site, which might explain why secretory Ig

168 d via the polymeric immunoglobulin receptor (pIgR).

169 receptor, polymeric immunoglobulin receptor (pIgR).

170 m via the polymeric immunoglobulin receptor (pIgR).

171 ed by the polymeric immunoglobulin receptor (pIgR).

172 ed by the polymeric immunoglobulin receptor (pIgR).

173 , via the polymeric immunoglobulin receptor (pIgR).

174 in is the polymeric immunoglobulin receptor (pIgR).

175 (pIgA) is transcytosed by the pIgA receptor (pIgR) across mucosal epithelial cells.

176 The role of the polymeric receptor (pIgR) is to transport polymeric IgA across various mucos

177 d for the polymeric immunoglobulin receptor [pIgR]), apical recycling of pIgR-IgA, and accumulation o

178 that signaling through TLRs may up-regulate pIgR expression by intestinal epithelial cells and thus

179 ling through LPS/TLR4 appears to up-regulate pIgR expression while minimizing proinflammatory respons

180 , studies demonstrate that IL-4 up-regulates pIgR production via Janus kinase/signal transducers and

181 Consistent with our previous work, sIgA, pIgR, and IL-4 decreased with PN, whereas the addition o

182 We found that detergent-solubilized pIgR binds to CaM-agarose in a Ca(2+)-dependent fashion,

183 ion is necessary and sufficient to stimulate pIgR transcytosis.

184 binding to the pIgR control dIgA-stimulated pIgR transcytosis.

185 ring PN, we hypothesized that the suppressed pIgR is a result of decreased JAK-1 and STAT-6 phosphory

186 gulated levels of pIgR mRNA and cell surface pIgR protein.

187 ntrols, and assayed for IgA1/IgA2 synthesis, pIgR expression, production of secretory component (SC),

188 membrane, and delivery of newly synthesized pIgR from the Golgi to the basolateral membrane were all

189 nvolved in high-affinity binding to the T560 pIgR.

190 In this study, we demonstrate that pIgR can play a critical role in intestinal defense agai

191 affected by pIgR deficiency, indicating that pIgR had no physiologic role when lower luminal IgA leve

192 and a secretory protein, gp80, we show that pIgR and gp80 protein synthesis and delivery are increas

193 These findings show that pIgR/SIgA deficiency in the airways leads to persistent

194 ation of luminal cholera toxin, suggest that pIgR is essential in intestinal defense against pathogen

195 Our results suggest that pIgR-mediated transcytosis of antagonistic antibodies in

196 These results suggest that pIgR-mediated transcytosis of pIgA-EBV through epitheliu

197 o-2-naphthalenesulfonamide), suggesting that pIgR binding to CaM is specific.

198 Although the pIgR is constitutively transcytosed in the absence of li

199 present, because recycling receptors and the pIgR were coisolated on the same elements.

200 suggest that ligand-induced signaling by the pIgR may regulate membrane traffic via well-known second

201 ions, but which were not transcytosed by the pIgR, did not inhibit intracellular HIV replication, nor

202 s that are both bound and transported by the pIgR, this study provides evidence that the pIgR-mediate

203 isotype-specific and was not mediated by the pIgR.

204 ss the epithelium, a process mediated by the pIgR.

205 main swap" mutants, the binding site for the pIgR on dimeric IgA (dIgA) was localized to the Calpha3

206 represented a potential binding site for the pIgR.

207 ting that an IgA receptor, distinct from the pIgR, asialoglycoprotein receptor, galactosyltransferase

208 associated with evolutionary changes in the pIgR protein.

209 These data localize the pIgR binding site on dimeric human IgA to this loop stru

210 mbrane-proximal 17-amino acid segment of the pIgR cytoplasmic tail.

211 Interestingly, the large fourth exon of the pIgR gene encodes two immunoglobulin-like extracellular

212 extracellular, ligand-binding portion of the pIgR is proteolytically cleaved.

213 secretory component (SC), the portion of the pIgR that remains bound to pig in secretions, and immuno

214 c physical and functional association of the pIgR with p62yes in rodent liver.

215 y which cytokines regulate expression of the pIgR, a central player in mucosal immunity.

216 component, the extracellular portion of the pIgR, linked to human alpha1-antitrypsin is effectively

217 nscriptional regulation of expression of the pIgR.

218 nding of dIgA stimulates transcytosis of the pIgR.

219 In addition, we replaced the pIgR's transmembrane domain with that of glycophorin A t

220 ing of dIgA to the pIgR, indicating that the pIgR can transduce a signal to the cytoplasmic machinery

221 pIgR, this study provides evidence that the pIgR-mediated mucosal secretion system may represent a m

222 ort of green fluorescent protein through the pIgR-specific cellular transcytosis system.

223 We report that dIgA binding to the pIgR causes activation of protein kinase C (PKC) and rel

224 that are activated upon dIgA binding to the pIgR control dIgA-stimulated pIgR transcytosis.

225 conclude that binding of dimeric IgA to the pIgR induces its dimerization and that this dimerization

226 e recently reported that dIgA binding to the pIgR induces translocation of protein kinase C, producti

227 second signal depends on dIgA binding to the pIgR solely at the basolateral surface and the ability o

228 osis is stimulated by binding of dIgA to the pIgR, indicating that the pIgR can transduce a signal to

229 , using a protein that binds directly to the pIgR, Streptococcus pneumoniae can co-opt the transcytos

230 ary epithelial cells of PBC patients via the pIgR and complex with PDC-E2, thereby potentially contri

231 suggesting that binding can occur while the pIgR is in intact membranes.

232 ciation of tyrosine kinase activity with the pIgR and in transcytosis of pIgA.

233 This pIgR defect was associated with reduced levels of SC (P

234 ata suggest that during transcytosis through pIgR-positive cells, exposure to PDC-E2-specific dimeric

235 -1 and STAT-6, resulting in increased tissue pIgR and luminal IgA.

236 y an important role in bacterial adhesion to pIgR.

237 here to and invade human cells by binding to pIgR.

238 Binding of dIgA to pIgR at the basolateral surface stimulates subsequent tr

239 Binding of dIgA to pIgR causes a dissociation of the interaction with rab3b

240 n this area abrogated the binding of dIgA to pIgR, whereas adjacent substitutions in a beta-strand im

241 Binding of pIgA to pIgR stimulates transcytosis of the pIgA-pIgR complex vi

242 sity of recycling receptors and transcytotic pIgR in RRC membranes was similar to that in early endos

243 Finally, treating pIgR with a reducing agent abolished CbpA binding, sugge

244 owever, other biological functions for trout pIgR or trout secretory component (tSC) remain unknown.

245 Rainbow trout pIgR is known to transport IgT and IgM across epithelia.

246 However, binding of CaM to various pIgR mutants suggests that CaM binding is not necessary

247 gA-EBV complexes in the blood of mice, where pIgR-mediated transcytosis of IgA immune complexes throu

248 IgR expression was strongly induced, whereas pIgR expression and IgA-transcytosis capacity were decre

249 pendently inhibited pIgR production, whereas pIgR increased on blockade of TGF-beta1 activity during

250 canine kidney (MDCK) cells transfected with pIgR to determine the effect on viral antigen expression