Prolactin Up-Regulates Cathepsin B and D Expression in Minor Salivary Glands of Patients with Sjögren's Syndrome

Steinfeld, Serge; Maho, Arielle; Chaboteaux, Carole; Daelemans, Philippe; Pochet, Roland; Appelboom, Thierry; Kiss, Róbert

doi:10.1038/labinvest.3780181

Cited by 26 publications

(15 citation statements)

References 43 publications

(43 reference statements)

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“…Cathepsin B levels may be associated with cell differentiation (reviewed in Yan et al, 1998). Cathepsin B was not detected immunohistochemically in normal minor salivary glands (Steinfeld et al, 2000). However, minor glands in organotypic culture expressed significant levels of cathepsin B, primarily in the ducts, and these levels were substantially increased by treatment with prolactin.…”

Section: (I) Properties and Tissue Distributionmentioning

confidence: 91%

Cysteine Peptidases of Mammals: Their Biological Roles and Potential Effects in the Oral Cavity and Other Tissues in Health and Disease

Dickinson

2002

Critical Reviews in Oral Biology & Medicine

159

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Cysteine peptidases (CPs) are phylogenetically ubiquitous enzymes that can be classified into clans of evolutionarily independent proteins based on the structural organization of the active site. In mammals, two of the major clans represented in the genome are: the CA clan, whose members share a structure and evolutionary history with papain; and the CD clan, which includes the legumains and caspases. This review focuses on the properties of these enzymes, with an emphasis on their potential roles in the oral cavity. The human genome encodes at least (but possibly no more than) 11 distinct enzymes, called cathepsins, that are members of the papain family C1A. Ten of these are present in rodents, which also carry additional genes encoding other cathepsins and cathepsin-like proteins. Human cathepsins are best known from the ubiquitously expressed lysosomal cathepsins B, H, and L, and dipeptidyl peptidase I (DPP I), which until recently were considered to mediate primarily "housekeeping" functions in the cell. However, mutations in DPP I have now been shown to underlie Papillon-Lefèvre syndrome and pre-pubertal periodontitis. Other cathepsins are involved in tissue-specific functions such as bone remodeling, but relatively little is known about the functions of several recently discovered enzymes. Collectively, CPs participate in multiple host systems that are active in health and in disease. They are involved in tissue remodeling and turnover of the extracellular matrix, immune system function, and modulation and alteration of cell function. Intracellularly, CPs function in diverse processes including normal protein turnover, antigen and proprotein processing, and apoptosis. Extracellularly, they can contribute directly to the degradation of foreign proteins and the extracellular matrix. However, CPs can also participate in proteolytic cascades that amplify the degradative capacity, potentially leading to pathological damage, and facilitating the penetration of tissues by cancer cells. We know relatively little regarding the role of human CPs in the oral cavity in health or disease. Most studies to date have focused on the potential use of the lysosomal enzymes as markers for periodontal disease activity. Human saliva contains high levels of cystatins, which are potent CP inhibitors. Although these proteins are presumed to serve a protective function, their in vivo targets are unknown, and it remains to be discovered whether they serve to control any human CP activity.

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Section: (I) Properties and Tissue Distributionmentioning

confidence: 91%

Cysteine Peptidases of Mammals: Their Biological Roles and Potential Effects in the Oral Cavity and Other Tissues in Health and Disease

Dickinson

2002

Critical Reviews in Oral Biology & Medicine

159

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“…Cathepsin D immunoreactivity was considerably greater in both the acini and the ducts of patients with SS as compared with control subjects. Treatment of both healthy and SS minor salivary glands with PRL significantly enhanced cathepsin B and D. PRL, produced locally in SS patients, could play a role in the pathogenesis of primary SS [62].…”

Section: Prolactin and Rheumatoid Arthritismentioning

confidence: 98%

Prolactin and Autoimmunity

Jara

Medina

Saavedra

et al. 2009

Clinic Rev Allerg Immunol

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The relationship between prolactin and the immune system has been demonstrated in the last two decades, opening new windows in the field of the immunoendocrinology. Prolactin has an important role in the innate and adaptive immune response. Increased prolactin levels have been described in autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, Sjögren syndrome, and systemic sclerosis among others. Hyperprolactinemia is associated with active disease and organ involvement in systemic lupus erythematosus. Therefore, prolactin is an integral member of the immunoneuroendocrinology network and seems to have a role in pathogenesis of autoimmune diseases. Few controlled studies of dopamine agonist treatment in humans with autoimmune disease have been conducted only in systemic lupus erythematosus patients, which support the potential efficacy of such agents even during pregnancy and postpartum. Further studies are necessary to elucidate the mechanisms by which prolactin affects autoimmune disease activity, increase the inflammatory mechanism, and determine the role of anti-prolactinemic drugs to regulate the immune/inflammatory process.

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“…Other possible candidate genes include alpha-fodrin [45], beta-fodrin [46], Sjögren's 56 [47], ABCA1 [48], P230 trans Golgi network protein [49], 97 kD protein associated with Golgi complex [50], alpha-amylase [51], and the muscarinic-3 receptor [52]. In addition, there are protein expression changes that have been found in SS, including the cysteinerich secretory protein-3 [53], aquaporin-5 [54], aquaporin-1 [55], cyclooxygenase-1 [56], prolactin, and cathepsin B and D [57]. The genes responsible for effects in the nonobese diabetic mouse model of SS on mouse chromosome 1 [58•], 3 [59], and 4 [60] would become candidates when the genes are identified.…”

Section: Other Candidate Genesmentioning

confidence: 99%

The genetics of primary Sjögren’s syndrome

Sawalha¹,

Potts²,

Schmid³

et al. 2003

Curr Rheumatol Rep

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Primary Sjögren's syndrome is an autoimmune disease characterized clinically by dryness of the eyes and mouth. The use of different classification criteria for primary Sjögren's syndrome has led to dramatically different estimates of prevalence and incidence. Despite this, several genetic and environmental factors are thought to play a role in the susceptibility to primary Sjögren's syndrome, as is the current conceptual formulation of the pathogenesis of many other autoimmune maladies. Primary Sjögren's syndrome appears a complicated polygenic disorder with many genes interacting with environmental factors. Similar to many other polygenic autoimmune rheumatic diseases, human leukocyte antigen associations have been reported and confirmed. Additionally, other non-human leukocyte antigen candidate genes have been reported to reveal association with primary Sjögren's syndrome, but, in general, these effects are not confirmed. The authors review the human leukocyte antigen and non-human leukocyte antigen genetic associations herewith, knowing that new technologies are providing access to the entire genome for association studies. No doubt a much more comprehensive description of the genetics of this disorder will soon emerge.

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Prolactin Up-Regulates Cathepsin B and D Expression in Minor Salivary Glands of Patients with Sjögren's Syndrome

Cited by 26 publications

References 43 publications

Cysteine Peptidases of Mammals: Their Biological Roles and Potential Effects in the Oral Cavity and Other Tissues in Health and Disease

Cysteine Peptidases of Mammals: Their Biological Roles and Potential Effects in the Oral Cavity and Other Tissues in Health and Disease

Prolactin and Autoimmunity

The genetics of primary Sjögren’s syndrome

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