Abstract
S100A8 and S100A9 constitute a heterodimeric protein, calprotectin. The mRNAs of S100A8 and S100A9, being expressed at minimal levels in the submandibular and parotid glands (SMG and PG, respectively) of C3H/HeN mice, were induced strongly and transiently by lipopolysaccharide (LPS). Among the mRNAs of members of the S100 protein family examined, those of S100A8 and S100A9 were specifically induced by LPS in the salivary glands. The induction was assumed to be mediated via toll-like receptor 4 (TLR4), since their elevation was limited in C3H/HeJ mice, a TLR4-mutant strain. These proteins became expressed in the granular convoluted tubular cells and striated duct cells in the SMG, and in both acinar and duct cells in the PG (all in the cytoplasm). The salivary calprotectin level was not increased by LPS treatment, implying that elevated calprotectin was not secreted into the saliva and that they may function in microcellular environment of the salivary gland.
Similar content being viewed by others
Abbreviations
- DAPI:
-
4′, 6-diamidoino-2-phenylindole dihydrochloride
- GCT:
-
Granular convoluted tubule
- IL:
-
Interleukin
- ME:
-
Medium Electroendosmosis
- NF-κB:
-
Nuclear factor-κB
- Nod1:
-
Nucleotide-binding oligomerization domain-containing protein 1
- PG:
-
Parotid gland
- PBS:
-
Phosphate-buffered saline
- PI:
-
Propidium iodide
- RT-PCR:
-
Reverse transcriptase-polymerase chain reaction
- SD:
-
Striated duct
- SMG:
-
Submandibular gland
- TLR4:
-
Toll-like receptor 4
- TNF-α:
-
Tumor necrosis factor-α
REFERENCES
Eckert, R.L., A.M. Broome, M. Ruse, N. Robinson, D. Ryan, and K. Lee. 2004. S100 proteins in the epidermis. Journal of Investigative Dermatology 123: 23–33.
Donato, R. 2001. S100: A multigenic family of calcium-modulated proteins of the EF-hand type with intracellular and extracellular functional roles. The International Journal of Biochemistry & Cell Biology 33: 637–668.
Marenholz, I., C.W. Heizmann, and G. Fritz. 2004. S100 proteins in mouse and man: from evolution to function and pathology (including an update of the nomenclature). Biochemical and Biophysical Research Communications 322: 1111–1122.
Hsu, K., C. Champaiboon, B.D. Guenther, B.S. Sorenson, A. Khammanivong, K.F. Ross, C.L. Geczy, and M.C. Herzberg. 2009. Anti-infective protective properties of S100 calgranulins. Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry 8: 290–305.
Stříž, I., and I. Trebichavský. 2004. Calprotectin—a pleiotropic molecule in acute and chronic inflammation. Physiological Research 53: 245–253.
Pouliot, P., I. Plante, M.-A. Raquil, P.A. Tessier, and M. Olivier. 2008. Myeloid-related proteins rapidly modulate macrophage nitric oxide production during innate immune response. Journal of Immunology 181: 3595–3601.
Ryckman, C., K. Vandal, P. Roulean, M. Talbot, and P.A. Tessier. 2003. Proinflammatory activities of S100: Proteins S100A8, S100A9, and S100A8/A9 induce neutrophil chemotaxis and adhesion. Journal of Immunology 170: 3233–3242.
Newton, R.A., and N. Hogg. 1998. The human S100 protein MRP-14 is a novel activator of the β2 integrin Mac-1 on neutrophils. Journal of Immunology 160: 1427–1435.
Hofmann, M.A., S. Drury, C. Fu, W. Qu, A. Taguchi, Y. Lu, C. Avila, N. Kambham, A. Bierhaus, P. Nawroth, M.F. Neurath, T. Slattery, D. Beach, J. McClary, M. Nagashima, J. Morser, D. Stern, and A.M. Schmidt. 1999. RAGE mediates a novel proinflammatory axis: A central cell surface receptor for S100/calgranulin polypeptides. Cell 97: 889–901.
Arumugam, T., D.M. Simeone, A.M. Schmidt, and C.D. Logsdon. 2004. S100P stimulates cell proliferation and survival via receptor for activated glycation end products (RAGE). The Journal of Biological Chemistry 279: 5059–5065.
Zenz, R., R. Eferl, L. Kenner, L. Florin, L. Hummerich, D. Mehic, H. Scheuch, R. Zenz, R. Eferl, L. Kenner, L. Florin, L. Hummerich, D. Mehic, and H. Scheuch. 2005. Psoriasis-like skin disease and arthritis caused by inducible epidermal deletion of Jun proteins. Nature 437: 369–375.
Vogl, T., K. Tenbrock, S. Ludwig, N. Leukert, C. Ehrhardt, M.A. van Zoelen, W. Nacken, D. Foell, T. van der Poll, C. Sorg, and J. Roth. 2007. Mrp8 and Mrp14 are endogenous activators of Toll-like receptor 4, promoting lethal, endotoxin-induced shock. Nature Medicine 13: 1042–1049.
Kido, J., R. Kido, M.K. Suryono, M.K. Fagerhol, and T. Nagata. 2003. Calprotectin release from human neutrophils is induced by Porphyromonas gingivalis lipopolysaccharide via the CD-14-Toll-like receptor-nuclear factor κB pathway. Journal of Periodontal Research 38: 557–563.
Brun, J.G., M. Cuida, H. Jacobsen, R. Kloster, A.C. Johannesen, H.M. Høyeraal, and R. Jonsson. 1994. Sjögren’s syndrome in inflammatory rheumatic diseases: Analysis of the leukocyte protein calprotectin in plasma and saliva. Scandinavian Journal of Rheumatology 23: 114–118.
Cuida, M., A.K. Halse, A.C. Johannessen, T. Tynning, and R. Jonsson. 1997. Indicators of salivary gland inflammation in primary Sjogren’s syndrome. European Journal of Oral Sciences 105: 228–233.
Kojima, T., E. Andersen, J.C. Sanchez, M.R. Wilkins, D.F. Hochstrasser, W.F. Pralong, and G. Cimasoni. 2000. Human gingival crevicular fluid contains MRP8 (S100A8) and MRP14 (S100A9), two calcium-binding proteins of the S100 family. Journal of Dental Research 79: 740–747.
Lundy, F.T., R. Chalk, P.J. Lamey, C. Shaw, and G.J. Linden. 2000. Identification of MRP-8 (calgranulin A) as a major responsive protein in chronic periodontitis. The Journal of Pathology 192: 540–544.
Brandtzaeg, P., I. Dale, and M.K. Fagerhol. 1987. Distribution of a formalin-resistant myelomonocytic antigen (L1) in human tissues. II. Normal and aberrant occurrence in various epithelia. American Journal of Clinical Pathology 87: 700–707.
Sahasrabudhe, K.S., J.R. Kimball, T.H. Morton, A. Weinberg, and B.A. Dale. 2000. Expression of the antimicrobial peptide, human β-defensin 1, in duct cells of minor salivary glands and detection in saliva. Journal of Dental Research 79: 1669–1674.
Dommisch, H., J. Winter, Y. Acil, A. Dunsche, M. Tiemann, and S. Jepsen. 2005. Human β–defensin (hBD-1, -2) expression in dental pulp. Oral Microbiology and Immunology 20: 163–166.
Yao, C., X. Li, K. Murdiastuti, C. Kosugi-Tanaka, T. Akamatsu, N. Kanamori, and K. Hosoi. 2005. Lipopolysaccharide-induced elevation and secretion of interleukin-1β in the submandibular gland of male mice. Immunology 116: 213–222.
Mandel, I.D. 1987. The functions of saliva. Journal of Dental Research 66: 623–627.
Hashimoto, J., K. Yamada, K. Ogata, Y. Takai, and M. Mori. 1992. Immunoreaction of keratin, actin, S100 protein and rat-EGF in duct-ligated rat salivary glands. Journal of Oral Pathology and Medicine 21: 214–220.
Hashimoto, J., N. Jayasinghe, M. Kunikata, Y. Takai, and M. Mori. 1992. Immunoreactivity of calmodulin, S100 protein alpha and beta subunits in rat submandibular glands. Archives d’Anatomie et de Cytologie Pathologiques 40: 79–87.
Yao, C., W. Wei, X. Li, and K. Hosoi. 2005. Acute phase protein induction by experimental inflammation in the salivary gland. Journal of Oral Pathology & Medicine 34: 364–367.
Yao, C., P. Nunuk, M.R. Karabasil, A. Azlina, P. Javkhlan, T. Hasegawa, T. Akamatsu, T. Hosoi, K. Ozawa, and K. Hosoi. 2010. Potential down-regulation of salivary gland AQP5 by LPS via cross-coupling of NF-κB and p-c-Jun/c-Fos. The American Journal of Pathology 177: 724–734.
Hiroshima, Y., M. Bando, M. Kataoka, Y. Shinohara, M.C. Herzberg, K.F. Ross, Y. Inagaki, T. Nagata, and J. Kido. 2010. Shosaikoto increases calprotectin expression in human oral epithelial cells. Journal of Periodontal Research 45: 79–86.
Cataisson, C., A.J. Pearson, S. Torgerson, S.A. Nedospasov, and S.H. Yuspa. 2005. Protein kinase C α-mediated chemotaxis of neutrophils requires NF-κB activity but is independent of TNF α signaling in mouse skin in vivo. Journal of Immunology 174: 1686–1692.
Ridinger, K., E.C. Ilg, F.K. Niggli, C.W. Heizmann, and B.W. Schafer. 1998. Clustered organization of S100 genes in human and mouse. Biochimica et Biophysica Acta 1448: 254–263.
Ka, S.M., A. Rifai, J.H. Chen, C.W. Cheng, H.A. Shui, H.S. Lee, Y.F. Lin, L.F. Hsu, and A. Chen. 2006. Glomerular crescent-related biomarkers in a murine model of chronic graft versus host disease. Nephrology, Dialysis, Transplantation 21: 288–298.
Webb, M., E.D. Emberley, M. Lizardo, S. Alowami, G. Qing, A. Alfia’ar, L.J. Snell-Curtis, Y. Niu, A. Civetta, Y. Myal, R. Shiu, L.C. Murphy, and P.H. Watson. 2005. Expression analysis of the mouse S100A7/psoriasin gene in skin inflammation and mammary tumorigenesis. BMC Cancer 5: 17. doi:10.1186/1471-2407-5-17.
Dudley, K.J., K. Revill, P. Whitby, R.N. Clayton, and W.E. Farrell. 2008. Genome-wide analysis in a mature Dnmt1 knockdown model identifies epigenetically silenced genes in primary human pituitary tumors. Molecular Cancer Research 6: 1567–1574.
Yoshikawa, T., Y. Nagasugi, T. Azuma, M. Kato, S. Sugano, K. Hashimoto, Y. Masuho, M. Muramatsu, and N. Seki. 2000. Isolation of novel mouse genes differentially expressed in brain using cDNA microarray. Biochemical and Biophysical Research Communications 275: 532–537.
Rodriguez, A., M. Hilvo, L. Kytömäki, R.E. Fleming, R.S. Britton, B.R. Bacon, and S. Parkkila. 2007. Effects of iron loading on muscle: Genome-wide mRNA expression profiling in the mouse. BMC Genomics 8: 379. doi:10.1186/1471-2164-8-379.
Kocher, M., P.A. Kenny, E. Farram, K.B. Abdul Majid, J.J. Finlay-Jones, and C.L. Geczy. 1996. Functional chemotactic factor CP-10 and MRP-14 are abundant in murine abscesses. Infection and Immunity 64: 1342–1350.
Hosoi, K., S. Tsunasawa, K. Kurihara, H. Aoyama, T. Ueha, T. Murai, and F. Sakiyama. 1994. Identification of mK1, a true tissue (glandular) kallikrein of mouse submandibular gland: Tissue distribution and a comparison of kinin-releasing activity with other submandibular kallikreins. Journal of Biochemistry 115: 137–143.
Maruyama, S., K. Hosoi, T. Ueha, M. Tajima, S. Sato, and E.W. Gresik. 1993. Effects of female hormones and 3, 5, 3′-triiodothyronine or dexamethasone on induction of epidermal growth factor and proteinases F, D, A, and P in the submandibular glands of hypophysectomized male mice. Endocrinology 133: 1051–1060.
Kurabuchi, S., and K. Hosoi. 2009. Immunocytochemical study of granular duct cells with a hormonally enhanced granular cell phenotype in the mouse parotid gland. Odontology 97: 57–61.
Angiero, F., D. Sozzi, R. Seramondi, and M.G. Valente. 2009. Epithelial-myoepithelial carcinoma of the minor salivary glands: Immunohistochemical and morphological features. Anticancer Research 29: 4703–4709.
Weinreb, I., R.R. Seethala, J.L. Hunt, R. Chetty, I. Dardick, and B. Perez-Ordoñez. 2009. Intercalated duct lesions of salivary gland: A morphologic spectrum from hyperplasia to adenoma. The American Journal of Surgical Pathology 33: 1322–1329.
Okura, M., T. Hiranuma, G. Tominaga, H. Yoshioka, T. Aikawa, K. Shirasuna, and T. Matsuya. 1996. Expression of S-100 protein and glial fibrillary acidic protein in cultured submandibular gland epithelial cells and salivary gland tissues. Histogenetic implication for salivary gland tumors. American Journal of Pathology 148: 1709–1716.
Pechkovsky, D.V., O.M. Zalutskaya, G.L. Ivanov, and N.I. Misuno. 2000. Calprotectin (MRP8/14 protein complex) release during mycobacterial infection in vitro and in vivo. FEMS Immunology and Medical Microbiology 29: 27–33.
Poltorak, A., X. He, I. Smirnova, M.Y. Liu, C. Van Huffel, X. Du, D. Birdwell, E. Alejos, M. Silva, C. Galanos, M. Freudenberg, P. Ricciardi-Castagnoli, B. Layton, and B. Beutler. 1998. Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: Mutations in TLR4 gene. Science 282: 2085–2088.
Akira, S., and K. Takeda. 2004. Toll-like receptor signalling. Nature Reviews. Immunology 4: 499–511.
Inohara, N., Y. Ogura, F.F. Chen, A. Muto, and G. Nuñez. 2001. Human Nod1 confers responsiveness to bacterial lipopolysaccharides. The Journal of Biological Chemistry 276: 2551–2554.
Manitz, M.P., B. Horst, S. Seeliger, A. Strey, B.V. Skryabin, M. Gunzer, W. Frings, F. Schönlau, J. Roth, C. Sorg, and W. Nacken. 2003. Loss of S100A9 (MRP14) results in reduced interleukin-8-induced CD11b surface expression, a polarized microfilament system, and diminished responsiveness to chemoattractants in vitro. Molecular and Cellular Biology 23: 1034–1043.
Sweet, S.P., A.N. Denbury, and S.J. Challacombe. 2001. Salivary calprotectin levels are raised in patients with oral candidiasis or Sjögren’s syndrome but decreased by HIV infection Oral Microbiology and Immunology 16: 119–123.
Vogl, T., S. Ludwig, M. Goebeler, A. Strey, I.S. Thorey, R. Reichelt, D. Foell, V. Gerke, M.P. Manitz, W. Nacken, S. Werner, C. Sorg, and J. Roth. 2004. MRP8 and MRP14 control microtubule reorganization during transendothelial migration of phagocytes. Blood 104: 4260–4268.
Author information
Authors and Affiliations
Corresponding author
Additional information
This work was submitted to the Graduate School of Oral Sciences, The University of Tokushima as a part of a dissertation for the Doctorate of Philosophy Degree.
Rights and permissions
About this article
Cite this article
Javkhlan, P., Hiroshima, Y., Azlina, A. et al. Lipopolysaccharide-Mediated Induction of Calprotectin in the Submandibular and Parotid Glands of Mice. Inflammation 34, 668–680 (2011). https://doi.org/10.1007/s10753-010-9277-1
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10753-010-9277-1