NSD Overexpression in the Fat Body Increases Antimicrobial Peptide Production by the Immune Deficiency Pathway in <i>Drosophila</i>
Nuclear receptor-binding SET domain-containing protein 1 (NSD1) inactivation in tumor cells contributes to an immune-cold phenotype, indicating its potential association with immune disturbances. <i>Drosophila</i> NSD is a homolog of the human NSD1. Thus, in this study, we investigated t...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-05-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/24/9/8443 |
| _version_ | 1797602379041865728 |
|---|---|
| author | Chihyun Won Kyungju Nam Donghee Ko Byungjun Kang Im-Soon Lee |
| author_facet | Chihyun Won Kyungju Nam Donghee Ko Byungjun Kang Im-Soon Lee |
| author_sort | Chihyun Won |
| collection | DOAJ |
| description | Nuclear receptor-binding SET domain-containing protein 1 (NSD1) inactivation in tumor cells contributes to an immune-cold phenotype, indicating its potential association with immune disturbances. <i>Drosophila</i> NSD is a homolog of the human NSD1. Thus, in this study, we investigated the effect of NSD overexpression in the fat body, the central organ involved in <i>Drosophila</i> immune responses. Upon ectopic expression of NSD in the fat body, the mRNA levels of antimicrobial peptides increased. Using reporter constructs containing deletions of various NF-κB sites in the Attacin-A (<i>AttA</i>) promoter, we found that transcriptional activation by NSD is mainly mediated via the IMD pathway by activating Relish. Since the IMD pathway is required to resist Gram-negative bacterial infections, we further examined the effect of fat body-specific NSD overexpression on <i>Drosophila</i> immune defenses. Upon oral ingestion of Gram-negative <i>Pseudomonas entomophila</i>, the survival rate of the NSD-overexpressing larvae was higher than that of the wild type, suggesting a positive role of NSD in immune responses. Taken together, these results suggest the association of NSD with the IMD pathway and is thus expected to contribute to the elucidation of the molecular mechanisms of immune malfunction in various NSD1-associated human diseases. |
| first_indexed | 2024-03-11T04:15:16Z |
| format | Article |
| id | doaj.art-78e7a91fbafc4dc580e91689bcbc104c |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T04:15:16Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-78e7a91fbafc4dc580e91689bcbc104c2023-11-17T23:09:46ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-05-01249844310.3390/ijms24098443NSD Overexpression in the Fat Body Increases Antimicrobial Peptide Production by the Immune Deficiency Pathway in <i>Drosophila</i>Chihyun Won0Kyungju Nam1Donghee Ko2Byungjun Kang3Im-Soon Lee4Department of Biological Sciences, Konkuk University, Seoul 05029, Republic of KoreaDepartment of Biological Sciences, Konkuk University, Seoul 05029, Republic of KoreaDepartment of Biological Sciences, Konkuk University, Seoul 05029, Republic of KoreaDepartment of Biological Sciences, Konkuk University, Seoul 05029, Republic of KoreaDepartment of Biological Sciences, Konkuk University, Seoul 05029, Republic of KoreaNuclear receptor-binding SET domain-containing protein 1 (NSD1) inactivation in tumor cells contributes to an immune-cold phenotype, indicating its potential association with immune disturbances. <i>Drosophila</i> NSD is a homolog of the human NSD1. Thus, in this study, we investigated the effect of NSD overexpression in the fat body, the central organ involved in <i>Drosophila</i> immune responses. Upon ectopic expression of NSD in the fat body, the mRNA levels of antimicrobial peptides increased. Using reporter constructs containing deletions of various NF-κB sites in the Attacin-A (<i>AttA</i>) promoter, we found that transcriptional activation by NSD is mainly mediated via the IMD pathway by activating Relish. Since the IMD pathway is required to resist Gram-negative bacterial infections, we further examined the effect of fat body-specific NSD overexpression on <i>Drosophila</i> immune defenses. Upon oral ingestion of Gram-negative <i>Pseudomonas entomophila</i>, the survival rate of the NSD-overexpressing larvae was higher than that of the wild type, suggesting a positive role of NSD in immune responses. Taken together, these results suggest the association of NSD with the IMD pathway and is thus expected to contribute to the elucidation of the molecular mechanisms of immune malfunction in various NSD1-associated human diseases.https://www.mdpi.com/1422-0067/24/9/8443NSDSOTOSIMD<i>Drosophila</i> AMPNF-κB |
| spellingShingle | Chihyun Won Kyungju Nam Donghee Ko Byungjun Kang Im-Soon Lee NSD Overexpression in the Fat Body Increases Antimicrobial Peptide Production by the Immune Deficiency Pathway in <i>Drosophila</i> International Journal of Molecular Sciences NSD SOTOS IMD <i>Drosophila</i> AMP NF-κB |
| title | NSD Overexpression in the Fat Body Increases Antimicrobial Peptide Production by the Immune Deficiency Pathway in <i>Drosophila</i> |
| title_full | NSD Overexpression in the Fat Body Increases Antimicrobial Peptide Production by the Immune Deficiency Pathway in <i>Drosophila</i> |
| title_fullStr | NSD Overexpression in the Fat Body Increases Antimicrobial Peptide Production by the Immune Deficiency Pathway in <i>Drosophila</i> |
| title_full_unstemmed | NSD Overexpression in the Fat Body Increases Antimicrobial Peptide Production by the Immune Deficiency Pathway in <i>Drosophila</i> |
| title_short | NSD Overexpression in the Fat Body Increases Antimicrobial Peptide Production by the Immune Deficiency Pathway in <i>Drosophila</i> |
| title_sort | nsd overexpression in the fat body increases antimicrobial peptide production by the immune deficiency pathway in i drosophila i |
| topic | NSD SOTOS IMD <i>Drosophila</i> AMP NF-κB |
| url | https://www.mdpi.com/1422-0067/24/9/8443 |
| work_keys_str_mv | AT chihyunwon nsdoverexpressioninthefatbodyincreasesantimicrobialpeptideproductionbytheimmunedeficiencypathwayinidrosophilai AT kyungjunam nsdoverexpressioninthefatbodyincreasesantimicrobialpeptideproductionbytheimmunedeficiencypathwayinidrosophilai AT dongheeko nsdoverexpressioninthefatbodyincreasesantimicrobialpeptideproductionbytheimmunedeficiencypathwayinidrosophilai AT byungjunkang nsdoverexpressioninthefatbodyincreasesantimicrobialpeptideproductionbytheimmunedeficiencypathwayinidrosophilai AT imsoonlee nsdoverexpressioninthefatbodyincreasesantimicrobialpeptideproductionbytheimmunedeficiencypathwayinidrosophilai |