Nucleotide-binding oligomerization domain protein-1 is expressed and involved in the inflammatory response in human sebocytes
Sebocytes express Toll-like receptors (TLRs) and nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs), which participate in the innate immune response of the skin. Although the roles of TLRs and NLR family pyrin domain-containing 3 (NLRP3) in inflammatory responses in sebocytes have...
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Elsevier
2023-12-01
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Series: | Biochemistry and Biophysics Reports |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S2405580823001425 |
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author | Natsuko Kitajima Takahisa Nakajo Takeshi Katayoshi Kentaro Tsuji-Naito |
author_facet | Natsuko Kitajima Takahisa Nakajo Takeshi Katayoshi Kentaro Tsuji-Naito |
author_sort | Natsuko Kitajima |
collection | DOAJ |
description | Sebocytes express Toll-like receptors (TLRs) and nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs), which participate in the innate immune response of the skin. Although the roles of TLRs and NLR family pyrin domain-containing 3 (NLRP3) in inflammatory responses in sebocytes have been reported, the expression and functions of other NLR members, such as NOD protein-1 and -2 (NOD1 and NOD2, respectively), remain unclear. In this study, we showed that, in sebocytes, the expression of NOD1 is higher than that of NOD2, and that NOD1 is involved in inflammatory responses, such as the secretion of proinflammatory cytokines. A NOD1 agonist, L-alanyl-γ-D-glutamyl-meso-diaminopimelic acid (Tri-DAP) induced the expression and secretion of interleukin-8 (IL-8) and activated the nuclear factor-kappa B and mitogen-activated protein kinase signaling pathways. On the other hand, a NOD2 agonist, muramyl dipeptide, did not. Either inhibition with a NOD1 inhibitor, ML130, or knockdown of NOD1 expression abolished Tri-DAP-induced inflammatory responses, suggesting that NOD1 is involved in the immunogenic signaling system of sebocytes. Furthermore, Tri-DAP and an agonist of TLR2 or TLR4 additively increased IL-8 expression compared with each agonist alone. Our results reveal the role of NOD1 in the inflammatory responses of sebocytes and may provide a novel therapeutic target for sebaceous gland inflammatory diseases, such as acne vulgaris. |
first_indexed | 2024-03-09T07:33:50Z |
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id | doaj.art-0011728092374a77ac11d77d7e12bd6b |
institution | Directory Open Access Journal |
issn | 2405-5808 |
language | English |
last_indexed | 2024-03-09T07:33:50Z |
publishDate | 2023-12-01 |
publisher | Elsevier |
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series | Biochemistry and Biophysics Reports |
spelling | doaj.art-0011728092374a77ac11d77d7e12bd6b2023-12-03T05:41:55ZengElsevierBiochemistry and Biophysics Reports2405-58082023-12-0136101561Nucleotide-binding oligomerization domain protein-1 is expressed and involved in the inflammatory response in human sebocytesNatsuko Kitajima0Takahisa Nakajo1Takeshi Katayoshi2Kentaro Tsuji-Naito3DHC Corporation Laboratories, Division 2, 2-42 Hamada, Mihama-ku, Chiba, 261-0025, JapanDHC Corporation Laboratories, Division 2, 2-42 Hamada, Mihama-ku, Chiba, 261-0025, JapanDHC Corporation Laboratories, Division 2, 2-42 Hamada, Mihama-ku, Chiba, 261-0025, JapanCorresponding author.; DHC Corporation Laboratories, Division 2, 2-42 Hamada, Mihama-ku, Chiba, 261-0025, JapanSebocytes express Toll-like receptors (TLRs) and nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs), which participate in the innate immune response of the skin. Although the roles of TLRs and NLR family pyrin domain-containing 3 (NLRP3) in inflammatory responses in sebocytes have been reported, the expression and functions of other NLR members, such as NOD protein-1 and -2 (NOD1 and NOD2, respectively), remain unclear. In this study, we showed that, in sebocytes, the expression of NOD1 is higher than that of NOD2, and that NOD1 is involved in inflammatory responses, such as the secretion of proinflammatory cytokines. A NOD1 agonist, L-alanyl-γ-D-glutamyl-meso-diaminopimelic acid (Tri-DAP) induced the expression and secretion of interleukin-8 (IL-8) and activated the nuclear factor-kappa B and mitogen-activated protein kinase signaling pathways. On the other hand, a NOD2 agonist, muramyl dipeptide, did not. Either inhibition with a NOD1 inhibitor, ML130, or knockdown of NOD1 expression abolished Tri-DAP-induced inflammatory responses, suggesting that NOD1 is involved in the immunogenic signaling system of sebocytes. Furthermore, Tri-DAP and an agonist of TLR2 or TLR4 additively increased IL-8 expression compared with each agonist alone. Our results reveal the role of NOD1 in the inflammatory responses of sebocytes and may provide a novel therapeutic target for sebaceous gland inflammatory diseases, such as acne vulgaris.http://www.sciencedirect.com/science/article/pii/S2405580823001425SebocytesNOD1Interleukin-8Inflammatory responseAcne vulgaris |
spellingShingle | Natsuko Kitajima Takahisa Nakajo Takeshi Katayoshi Kentaro Tsuji-Naito Nucleotide-binding oligomerization domain protein-1 is expressed and involved in the inflammatory response in human sebocytes Biochemistry and Biophysics Reports Sebocytes NOD1 Interleukin-8 Inflammatory response Acne vulgaris |
title | Nucleotide-binding oligomerization domain protein-1 is expressed and involved in the inflammatory response in human sebocytes |
title_full | Nucleotide-binding oligomerization domain protein-1 is expressed and involved in the inflammatory response in human sebocytes |
title_fullStr | Nucleotide-binding oligomerization domain protein-1 is expressed and involved in the inflammatory response in human sebocytes |
title_full_unstemmed | Nucleotide-binding oligomerization domain protein-1 is expressed and involved in the inflammatory response in human sebocytes |
title_short | Nucleotide-binding oligomerization domain protein-1 is expressed and involved in the inflammatory response in human sebocytes |
title_sort | nucleotide binding oligomerization domain protein 1 is expressed and involved in the inflammatory response in human sebocytes |
topic | Sebocytes NOD1 Interleukin-8 Inflammatory response Acne vulgaris |
url | http://www.sciencedirect.com/science/article/pii/S2405580823001425 |
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