Advances in Pathogenesis of Sjögren's Syndrome.

Sjögren's syndrome (SS) is a chronic autoimmune disease of unknown etiology that mainly involves exocrine glands. Patients present with dry mouth and eyes, fever, arthralgia, and other systemic symptoms. In severe cases, the quality of life of patients is affected. At present, there is no cure for SS, and the treatment options are extremely limited. In recent years, studies of patients and animal models have identified abnormalities of immune cell function and cytokines to be involved in SS. A systematic review of the literature may clarify the etiology and pathogenesis of SS, as well as provide a theoretical basis for the development of new drugs for the treatment of SS.

Enhancement of Apis mellifera L. Hypopharyngeal Gland using Hyphaene thebaica Ethanolic Extract as Supplement.

BACKGROUND AND OBJECTIVE: Hypopharyngeal gland (HPG) of Apis mellifera L. honey bee workers secrete the main proteinaceous substances, the royal jelly which acts a vital role in brood care by young workers and thus colony growth. Many factors may affect the development and function of the hypopharyngeal gland and consequently their role within the beehive. MATERIALS AND METHODS: Hyphaene thebaica fruit powder (500 g) was soaked in one litter of 70% ethanol for 3 days at room temperature, then filtered and concentrated to dryness with a rotary evaporator. Bioactive compounds and biological activity of doum ethanolic extract were characterized to measure the extent of safety. Samples of workers bee feeding with the extract concentrations (0.5 and 1%) at 6, 10 and 14 days were examined for head weight, body weight, soluble protein content, DNA fragmentation and hypopharyngeal glands histology, the data were analyzed using analysis of variance (ANOVA), Tukey's least significant difference. RESULTS: Ethanolic doum extract contains flavonoids (45.62 mg g-1) and phenolic (27.24 mg g-1) compounds, also possess antioxidant (147 µg mL-1), anti-inflammatory (119.8 µg mL-1) and antimicrobial activities. There was an elevation in soluble protein content and no DNA damage in the honey bee worker's genome after fourteen days of feeding. The histological studies exhibited no deformation in the structure of gland acini and an increase in gland size was detected. CONCLUSION: Ethanolic doum extract in the bee diet has a role in HPG enhancement. Studies on its safety profile and biological activities make it a good choice to attenuate honey bee diseases inside bee colonies.

Structural Identification, Synthesis and Biological Activity of Two Volatile Cyclic Dipeptides in a Terrestrial Vertebrate.

Single substances within complex vertebrate chemical signals could be physiologically or behaviourally active. However, the vast diversity in chemical structure, physical properties and molecular size of semiochemicals makes identifying pheromonally active compounds no easy task. Here, we identified two volatile cyclic dipeptides, cyclo(L-Leu-L-Pro) and cyclo(L-Pro-L-Pro), from the complex mixture of a chemical signal in terrestrial vertebrates (lizard genus Sceloporus), synthesised one of them and investigated their biological activity in male intra-specific communication. In a series of behavioural trials, lizards performed more chemosensory behaviour (tongue flicks, lip smacks and substrate lickings) when presented with the synthesised cyclo(L-Pro-L-Pro) chemical blend, compared to the controls, the cyclo(L-Leu-L-Pro) blend, or a combined blend with both cyclic dipeptides. The results suggest a potential semiochemical role of cyclo(L-Pro-L-Pro) and a modulating effect of cyclo(L-Leu-L-Pro) that may depend on the relative concentration of both compounds in the chemical signal. In addition, our results stress how minor compounds in complex mixtures can produce a meaningful behavioural response, how small differences in structural design are crucial for biological activity, and highlight the need for more studies to determine the complete functional landscape of biologically relevant compounds.

Thymol: Effects on reproductive biology and Gene's organ morphology in Rhipicephalus sanguineus sensu lato engorged females (Acari: Ixodidae).

Thymol is a monoterpene with proven acaricidal activity on different tick species and life stages. The objective of this work was to evaluate the effect of thymol on the reproductive biology of engorged females of Rhipicephalus sanguineus sensu lato and the morphological changes caused in the cells of the tubular and accessory glands of Gené's organ. The females were exposed to thymol by immersion. Seven groups were established: group I (distilled water), group II (30% ethanol), group III (thymol 1.25 mg/mL), group IV (thymol 2.5 mg/mL), group V (thymol 5.0 mg/mL), group VI (thymol 10.0 mg/mL), and group VII (thymol 20.0 mg/mL), with 20 replicates for each treatment. The ticks were kept in a BOD incubator at 27 ±â€¯1 °C and RH > 80 ±â€¯10%. Ten females from each group were evaluated daily until death, and the remaining ten were kept in the incubator under the same conditions for five days and then dissected for the removal of Gené's organ to note possible damage to cell morphology by scanning electron microscopy (SEM) and hematoxylin-eosin (HE) techniques. Thymol demonstrated 63% and 98% efficacy in groups VI (10.0 mg/mL) and VII (20.0 mg/mL), respectively. In these groups, the cells of the tubular and accessory glands of Gené's organ showed signs of damage: irregular eosin staining, rupture and deformation of the cellular limit, presence of fragmented nuclei, changes in cytoplasmic homogeneity and areas with deformation (folds) in the basal region.

Effect of long-term cadmium and copper intoxication on the efficiency of ampullate silk glands in false black widow Steatoda grossa (Theridiidae) spiders.

The aim of the study was to compare cellular effects of xenobiotic cadmium and biogenic copper in ampullate silk glands of false black widow Steatoda grossa spider after long-term exposure via ingestion under laboratory conditions. Both the level of selected detoxification parameters (glutathione S-transferase, catalase, and the level of total antioxidant capacity) and degree of genotoxic changes (comet assay) were determined in the silk glands. Additionally the contents of selected amino acids (L-Ala, L-Pro, L-His, L-Phe, DL-Ile, and DL-Asn) in the hunting webs produced by spiders of this species were assessed. The ability of S. grossa females to accumulate cadmium was higher than that for copper. Long-term exposure of spiders to copper did not change the level of detoxification parameters, and the level of DNA damage in the cells of ampullate silk glands was also low. Cadmium had a stronger prooxidative and genotoxic effect than copper in the cells of the analyzed silk glands. However, regardless of the type of metal used, no significant changes in the level of amino acids in silk were found. The obtained results confirmed the effectiveness of metal neutralization mechanisms in the body of the studied spider species, which results in the protection of the function of ampullate silk glands.

Contribution of HIV Infection, AIDS, and Antiretroviral Therapy to Exocrine Pathogenesis in Salivary and Lacrimal Glands.

The structure and function of exocrine glands are negatively affected by human immunodeficiency virus (HIV) infection and its co-morbidities, including innate and adaptive immune responses. At the same time, exocrine function may also be influenced by pharmacotherapies directed at the infectious agents. Here, we briefly review the role of the salivary glands and lacrimal glands in normal physiology and exocrine pathogenesis within the context of HIV infection and acquired immune deficiency syndrome (AIDS), including the contribution of antiretroviral therapies on both. Subsequently, we discuss the impact of HIV infection and the types of antiretroviral therapy on disease management and therapy development efforts.

Transcriptome analysis provides insights into the immunity function of venom glands in Pardosa pseudoannulata in responses to cadmium toxicity.

Due to some similarity of innate immunity between insects and mammals, the study of the molecular mechanism of innate immunity in insects has become a focus of research. However, the exact molecular and cellular basis of immune system in insect remains poorly understood. Characterization of the transcriptomic response to Cd of spider is an effective approach to understanding the innate immunity mechanisms. In this study, we carried out transcriptome sequencing and gene expression analyses to develop molecular resources for Pardosa pseudoannulata venom glands with and without Cd treatments. A total of 92,778 assembled unigenes and 237 Cd stress-associated differentially expressed genes between the Cd-treated and control groups were obtained. Expression profile analysis demonstrated that immunity-related genes involved in bacterial invasion of epithelial cells, leukocyte transendothelial migration, platelet activation, apoptosis, phagosome, and Rap1 signaling pathway were upregulated by Cd exposure, except the genes involved in PPAR signaling pathway were downregulated. Our results provide the first comprehensive transcriptome dataset of venom glands in P. pseudoannulata response to Cd, which is valuable for throws light on the immunotoxicity mechanism of Cd, and the innate immunity complexity.

Titanium nanoparticles influence the Akt/Tor signal pathway in the silkworm, Bombyx mori, silk gland.

Various nanoparticles, such as silver nanoparticles (AgNPs) and titanium nanoparticles (TiO2 NPs) are increasingly used in industrial processes. Because they are released into the environment, research into their influence on the biosphere is necessary. Among its other effects, dietary TiO2 NPs promotes silk protein synthesis in silkworms, which prompted our hypothesis that TiO2 NPs influence protein kinase B (Akt)/Target of rapamycin (Tor) signaling pathway (Akt/Tor) signaling in their silk glands. The Akt/Tor signaling pathway is a principle connector integrating cellular reactions to growth factors, metabolites, nutrients, protein synthesis, and stress. We tested our hypothesis by determining the influence of dietary TiO2 NPs (for 72 h) and, separately, of two Akt/Tor pathway inhibitors (LY294002 and rapamycin) on expression of Akt/Tor signaling pathway genes and proteins in the silk glands. TiO2 NPs treatments led to increased accumulation of mRNAs for Akt, Tor1 and Tor2 by 1.6-, 12.1-, and 4.8-fold. Dietary inhibitors led to 2.6- to 4-fold increases in mRNAs encoding Akt and substantial decreases in mRNAs encoding Tor1 and Tor2. Western blot analysis showed that dietary TiO2 NPs increased the phosphorylation of Akt and its downstream proteins. LY294002 treatments led to inhibition of Akt phosphorylation and its downstream proteins and rapamycin treatments similarly inhibited the phosphorylation of Tor-linked downstream proteins. These findings support our hypothesis that TiO2 NPs influence Akt/Tor signaling in silk glands. The significance of this work is identification of specific sites of TiO2 NPs actions.

Field-relevant doses of the systemic insecticide fipronil and fungicide pyraclostrobin impair mandibular and hypopharyngeal glands in nurse honeybees (Apis mellifera).

Global decreases in bee populations emphasize the importance of assessing how environmental stressors affect colony maintenance, especially considering the extreme task specialization observed in honeybee societies. Royal jelly, a protein secretion essential to colony nutrition, is produced by nurse honeybees, and development of bee mandibular glands, which comprise a reservoir surrounded by secretory cells and hypopharyngeal glands that are shaped by acini, is directly associated with production of this secretion. Here, we examined individual and combined effects of the systemic fungicide pyraclostrobin and insecticide fipronil in field-relevant doses (850 and 2.5 ppb, respectively) on mandibular and hypopharyngeal glands in nurse honeybees. Six days of pesticide treatment decreased secretory cell height in mandibular glands. When pyraclostrobin and fipronil were combined, the reservoir volume in mandibular glands also decreased. The total number of acini in hypopharyngeal glands was not affected, but pesticide treatment reduced the number of larger acini while increasing smaller acini. These morphological impairments appeared to reduce royal jelly secretion by nurse honeybees and consequently hampered colony maintenance. Overall, pesticide exposure in doses close to those experienced by bees in the field impaired brood-food glands in nurse honeybees, a change that could negatively influence development, survival, and colony maintenance.

Nuclear hormone receptor BmFTZ-F1 is involved in regulating the fibroin heavy chain gene in the silkworm, Bombyx mori.

BACKGROUND: The synthesis of silk protein is controlled by hormones. The expression of the nuclear hormone Bmftz-f1 in the posterior silk gland (PSG) is induced by 20-hydroxyecdysone in vivo and in vitro. However, whether Bmftz-f1 regulates silk protein expression is unknown. METHODS: In our study, western blotting and quantitative polymerase chain reactions were conducted to detect the expression of FTZ-F1 in the PSG. Electrophoretic mobility shift, chromatin immunoprecipitation, far-western blotting, bimolecular fluorescence complementation, and dual luciferase reporter assays were performed to investigate the effect of FTZ-F1 on the fibH promoter. RESULTS: (1) The expression of the hormone receptor BmFTZ-F1 was opposite to that of fibH. It was highly expressed in the PSG during the fourth molting stage and the beginning of the fifth instar, and then its expression decreased gradually until it disappeared at the end of the fifth instar and the wandering stage. (2) We identified a FTZ-F1 response element 390bp upstream of the transcription initiation site of the fibH promoter. (3) BmFTZ-F1 interacted with the basic helix-loop-helix transcription factor Bmdimm. (4) BmFTZ-F1 down-regulated fibH promoter activity and counteracted the effect of Bmdimm on fibH expression. CONCLUSIONS: Integrating these results, we conclude that BmFTZ-F1 regulates the transcription of fibH by binding to the FTZ-F1 response element in the fibH promoter and counteracts the effect of Bmdimm on fibH expression. GENERAL SIGNIFICANCE: These findings provide new insights into the mechanism of regulation of the silk protein gene.

Wnt Signaling Regulates Airway Epithelial Stem Cells in Adult Murine Submucosal Glands.

Wnt signaling is required for lineage commitment of glandular stem cells (SCs) during tracheal submucosal gland (SMG) morphogenesis from the surface airway epithelium (SAE). Whether similar Wnt-dependent processes coordinate SC expansion in adult SMGs following airway injury remains unknown. We found that two Wnt-reporters in mice (BAT-gal and TCF/Lef:H2B-GFP) are coexpressed in actively cycling SCs of primordial glandular placodes and in a small subset of adult SMG progenitor cells that enter the cell cycle 24 hours following airway injury. At homeostasis, these Wnt reporters showed nonoverlapping cellular patterns of expression in the SAE and SMGs. Following tracheal injury, proliferation was accompanied by dynamic changes in Wnt-reporter activity and the analysis of 56 Wnt-related signaling genes revealed unique temporal changes in expression within proximal (gland-containing) and distal (gland-free) portions of the trachea. Wnt stimulation in vivo and in vitro promoted epithelial proliferation in both SMGs and the SAE. Interestingly, slowly cycling nucleotide label-retaining cells (LRCs) of SMGs were spatially positioned near clusters of BAT-gal positive serous tubules. Isolation and culture of tet-inducible H2B-GFP LRCs demonstrated that SMG LRCs were more proliferative than SAE LRCs and culture expanded SMG-derived progenitor cells outcompeted SAE-derived progenitors in regeneration of tracheal xenograft epithelium using a clonal analysis competition assay. SMG-derived progenitors were also multipotent for cell types in the SAE and formed gland-like structures in xenografts. These studies demonstrate the importance of Wnt signals in modulating SC phenotypes within tracheal niches and provide new insight into phenotypic differences of SMG and SAE SCs. Stem Cells 2016;34:2758-2771.

Mimotope mimicking epidermal growth factor receptor alleviates mononuclear cell infiltration in exocrine glands induced by muscarinic acetylcholine 3 receptor.

The muscarinic type 3 receptor (M3R) plays a pivotal role in the pathogenesis of Sjögren's syndrome (SS). Characterization of the crosstalk between M3R and EGFR has been investigated in some human malignancies. In the current study, we sought to investigate whether EGFR mimic immunization could alleviate the abnormal immune responses in an experimental SS-like model triggered by M3R peptides. After immunization with the combination of mimotope and M3R peptide, the active immunization targeting EGFR induced by the mimotope could reduce the marked infiltration of mononuclear cells, the high titer of antibodies against M3R and the accumulation of crucial pro-inflammatory cytokines in mice immunized with M3R peptide. Mechanistic analysis showed that mimotope immunization could alleviate the autoimmune response through inhibiting mitochondrion-mediated anti-apoptosis and up-regulating the FAS apoptosis pathway. These results may help to clarify the role of M3R in the pathogenesis of SS and suggested that transactivation of the EGFR signaling pathway may help M3R activate the autoimmune response in the pathogenesis of SS.

Propagation of Intracellular Ca2+ Signals in Aged Exocrine Cells.

There is little information on the effects of aging in the propagation of calcium signals and its underlying mechanisms. We studied the effects of aging on propagation of Ca(2+) signals in pancreatic acinar cells. Fura-2 loaded cells isolated from young (3-4 months old) and aged (24 months old) mouse responded to acetylcholine (ACh) and cholecystokinin (CCK) with a polarized Ca(2+) response initiated at the secretory pole before spreading to the basal one. Aging slowed down the propagation of the response to ACh but enhanced the velocity of the CCK response. This pattern can be explained by the age-induced depolarization of mitochondria, because it can be reproduced in young cells by mitochondrial inhibitors. Aging also increased the role of acidic stores in the CCK signal, as judged by the folimycin-induced suppression of the polarization in aged but not in young cells. The involvement of ryanodine receptors in the ACh response was also enhanced, as indicated by the loss of polarization after the treatment with 8Br-cyclic ADP ribose. Therefore, we conclude that aging modifies differentially the propagation of ACh and CCK-evoked Ca(2+) signals through mitochondrial depolarization and changes in the role of the acidic Ca(2+) stores and ryanodine receptors in the initiation of the signals.

A feedback mechanism to control apoptosis occurs in the digestive gland of the oyster crassostrea gigas exposed to the paralytic shellfish toxins producer Alexandrium catenella.

To better understand the effect of Paralytic Shellfish Toxins (PSTs) accumulation in the digestive gland of the Pacific oyster, Crassostrea gigas, we experimentally exposed individual oysters for 48 h to a PSTs producer, the dinoflagellate Alexandrium catenella. In comparison to the effect of the non-toxic Alexandrium tamarense, on the eight apoptotic related genes tested, Bax and BI.1 were significantly upregulated in oysters exposed 48 h to A. catenella. Among the five detoxification related genes tested, the expression of cytochrome P450 (CYP1A) was shown to be correlated with toxin concentration in the digestive gland of oysters exposed to the toxic dinoflagellate. Beside this, we observed a significant increase in ROS production, a decrease in caspase-3/7 activity and normal percentage of apoptotic cells in this tissue. Taken together, these results suggest a feedback mechanism, which may occur in the digestive gland where BI.1 could play a key role in preventing the induction of apoptosis by PSTs. Moreover, the expression of CYP1A, Bax and BI.1 were found to be significantly correlated to the occurrence of natural toxic events, suggesting that the expression of these genes together could be used as biomarker to assess the biological responses of oysters to stress caused by PSTs.

Expression of CYP4 and GSTr genes in Venerupis philippinarum exposed to benzo(a)pyrene.

Bivalve molluscs, such as Venerupis philippinarum, are often used as bioindicators of environmental pollution since they can bioaccumulate a large variety of pollutants because of their filter feeding. The Polycyclic Aromatic Hydrocarbon (PAH) benzo(a)pyrene (B(a)P) is an important contaminant, commonly present in the marine environment. Pollutants are generally metabolized by enzymes of phase I, mainly CYPs enzymes, and by conjugation enzymes of phase II like GST. In this study, we investigated by Real Time PCR the expression of CYP4 and GSTr (GST class rho) in the digestive gland of V. philippinarum exposed to different concentrations of B(a)P for 24 h and after a 24 h depuration period. Accumulation of B(a)P by clams has been confirmed by the HPLC-FLD analyses. Moreover, HPLC-FLD analyses evidenced that after depuration, B(a)P concentrations decreased in animals subjected to 0.03 mg/l and 0.5mg/l exposures but did not decrease in animals subjected to 1mg/l exposure. B(a)P exposure and depuration did not cause histopathological lesions in the different organs. The analysis of GSTr expression in the digestive gland showed a significant increase in mRNA in animals subjected to 1 mg/l exposure, whereas the analysis of CYP4 expression did not evidence differences among treatments. Moreover, the expression of both genes did not exhibit any differences after the purification treatment. The results demonstrate that B(a)P significantly affects the expression of GSTr mRNA in the digestive gland of V. philippinarum and suggest that GSTr gene could play an important role in the biotransformation of B(a)P.

Dysfunctions of the translational machinery in digestive glands of mussels exposed to mercury ions.

Mercury is an element naturally occurring in the biosphere, but is also released into the environment by human activities, such as mining, smelting, and industrial discharge. Mercury is a biologically harmful element and any exposure of living organisms mainly due to contamination, can cause severe or even lethal side effects. In every form detected, elemental, inorganic, or organic, mercury exhibits toxicity associated with induced oxidative stress. Although the genotoxicity of mercury has been well demonstrated in mussels, little is known about its toxic effects on the translational machinery at the molecular level. To investigate possible effects, we exposed the common mussel Mytilus galloprovincialis in seawater supplemented by 30 µg/L Hg²âº for 15 days. We observed that Hg²âº was significantly accumulated in the digestive glands of mussels, reaching a level around 80 µg/g tissue (dry weight) at the 15th day of exposure. Exposure of mussels to Hg²âº resulted in failure of redox homeostasis, as reflected on lipid peroxidation levels and superoxide dismutase activity in glands, and micronucleus frequency in gills. Extracts from digestive glands after 15-day exposure to Hg²âº exhibited decreased tRNA aminoacylation ability and, moreover, a 70% reduction in the ability of 40S ribosomal subunits to form the 48S initiation ribosomal complex. A similar reduction was detected in the ability of ribosomes to translocate peptidyl-tRNA from the A-site to the P-site, an observation coinciding with the notion that regulation of protein synthesis by Hg²âº mainly occurs at the initiation and elongation stages of translation. A-site binding, peptidyl transferase activity, and termination of peptide chain synthesis underwent less pronounced but measurable reductions, a finding which explains why poly(Phe)-synthesis in ribosomes isolated from exposed mussels is reduced by 70%. In conclusion, Hg²âº apart from being a genotoxic ion acts as a modulator of protein synthesis in mussels, an observation probably related with its ability to induce oxidative stress.

Endometrial glands are essential for blastocyst implantation and decidualization in the mouse uterus.

Uterine glands and their secretions are hypothesized to be essential for blastocyst implantation and decidualization in the uterus of rodents and humans. One factor solely expressed by uterine glands in mice is leukemia inhibitory factor (LIF), and Lif null mice are infertile because of defective blastocyst attachment to the uterine luminal epithelium (LE). Progesterone treatment of neonatal mice permanently ablates differentiation of uterine glands, resulting in an aglandular uterus in the adult. Progesterone-induced uterine gland knockout (PUGKO) mice were used to investigate the biological role of uterine glands in blastocyst implantation and stromal cell decidualization. As compared to controls, PUGKO mice cycled normally but were infertile. Histological assessment of PUGKO uteri on Days 5.5 and 8.5 postmating found a hatched blastocyst apposed to an intact LE without evidence of implantation or stromal cell decidualization. Expression of several implantation-related factors, including Lif and PTGS2, were altered in the PUGKO uterus, whereas expression of steroid hormone receptors and their regulated genes was not different. Artificial decidualization was observed in the uteri of control but not PUGKO mice. Further, intrauterine administration of LIF failed to promote artificial decidualization in the uterus of PUGKO mice. Thus, uterine glands and their secretions have important biological roles in blastocyst implantation and stromal cell decidualization in the uterus.

Why mouse airway submucosal gland serous cells do not secrete fluid in response to cAMP stimulation.

Airway submucosal glands are important sites of cystic fibrosis transmembrane conductance regulator (CFTR) chloride (Cl(-)) channel expression and fluid secretion in the airway. Whereas both mouse and human submucosal glands and their serous acinar cells express CFTR, human glands and serous cells secrete much more robustly than mouse cells/glands in response to cAMP-generating agonists such as forskolin and vasoactive intestinal peptide. In this study, we examined mouse and human serous acinar cells to explain this difference and reveal further insights into the mechanisms of serous cell secretion. We found that mouse serous cells possess a robust cAMP-activated CFTR-dependent Cl(-) permeability, but they lack cAMP-activated calcium (Ca(2+)) signaling observed in human cells. Similar to human cells, basal K(+) conductance is extremely small in mouse acinar cells. Lack of cAMP-activated Ca(2+) signaling in mouse cells results in the absence of K(+) conductances required for secretion. However, cAMP activates CFTR-dependent fluid secretion during low-level cholinergic stimulation that fails to activate secretion on its own. Robust CFTR-dependent fluid secretion was also observed when cAMP stimulation was combined with direct pharmacological activation of epithelial K(+) channels with 1-ethyl-2-benzimidazolinone (EBIO). Our data suggest that mouse serous cells lack cAMP-mediated Ca(2+) signaling to activate basolateral membrane K(+) conductance, resulting in weak cAMP-driven serous cell fluid secretion, providing the likely explanation for reduced cAMP-driven secretion observed in mouse compared with human glands.

Comparative study on experimental autoimmune pancreatitis and its extrapancreatic involvement in mice.

OBJECTIVE: The objective of the study was to study the relationship between autoimmune pancreatitis (AIP) and colitis in C57BL/6 interleukin 10-deficient (IL-10KO) mice and to compare the extrapancreatic involvement of AIP between IL-10KO and MRL/Mp mice that developed pancreatitis. METHODS: Six-week-old female IL-10KO and MRL/Mp mice were injected intraperitoneally with polyinosinic polycytidylic acid (poly I:C) twice weekly for 8 or 12 weeks, respectively. The mice were killed, and the severity of inflammation in the pancreas, colon, liver, bile duct, and salivary gland was assessed using histological scoring systems. T-cell subsets derived from IL-10KO mice with pancreatitis were adoptively transferred into recombination activating gene 2-deficient mice. RESULTS: Administration of poly I:C induced pancreatitis and accelerated the development of colitis in IL-10KO mice. Pancreatitis was characterized by specific destruction of exocrine glands and the production of various autoantibodies. Involvement of the liver and bile duct was observed in both IL-10KO and MRL/Mp mice, but sialadenitis was present only in MRL/Mp mice. Adoptive transfer of CD4(+) T cells from AIP mice induced pancreatitis in recipient mice. CONCLUSIONS: Pancreatitis in IL-10KO mice resembles human type 1 AIP and is not associated with colitis. Genetic background may affect susceptibility to extrapancreatic involvement in type 1 AIP.

Chloride secretion by cultures of pig tracheal gland cells.

Malfunction of airway submucosal glands contributes to the pathology of cystic fibrosis (CF), and cell cultures of CF human airway glands show defects in Cl(-) and water transport. Recently, a transgenic pig model of CF (the CF pig) has been developed. Accordingly, we have developed cell cultures of pig airway gland epithelium for use in investigating alterations in gland function in CF. Our cultures form tight junctions (as evidenced by high transepithelial electrical resistance) and show high levels of active anion secretion (measured as amiloride-insensitive short-circuit current). In agreement with recent results on human airway glands, neurohumoral agents that elevate intracellular Ca(2+) potently stimulated anion secretion, while elevation of cAMP was comparatively ineffective. Our cultures express lactoferrin and lysozyme (serous gland cell markers) and MUC5B (the main mucin of airway glands). They are, therefore, potentially useful in determining if CF-related alterations in anion transport result in altered secretion of serous cell antimicrobial agents or mucus.