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Pharmacol."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Aberrant autoreactive B cell responses contribute to the pathogenesis of systemic lupus erythematosus (SLE). Currently, there is no safe and effective drug for intervention of SLE. Quinazoline derivative (N4-(4-phenoxyphenethyl)quinazoline-4,6-diamine, QNZ) is a NF-\u03baB inhibitor and has potent anti-inflammatory activity. However, it is unclear whether QNZ treatment can modulate B cell activation and SLE severity.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Splenic CD19<jats:sup>+<\/jats:sup> B cells were treated with QNZ (2, 10, or 50\u00a0nM) or paeoniflorin (200\u00a0\u03bcM, a positive control), and their activation and antigen presentation function-related molecule expression were examined by flow cytometry. MRL\/lpr lupus-prone mice were randomized and treated intraperitoneally with vehicle alone, 0.2\u00a0mg\/kg\/d QNZ or 1\u00a0mg\/kg\/d FK-506 (tacrolimus, a positive control) for 8\u00a0weeks. Their body weights and clinical symptoms were measured and the frequency of different subsets of splenic and lymph node activated B cells were quantified by flow cytometry. The degrees of kidney inflammation and glycogen deposition were examined by hematoxylin and eosin (H&amp;amp;E) and PAS staining. The levels of serum autoantibodies and renal IgG, complement C3 deposition were examined by ELISA and immunofluorescence.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> QNZ treatment significantly inhibited the activation and antigen presentation-related molecule expression of B cells <jats:italic>in vitro<\/jats:italic>. Similarly, treatment with QNZ significantly mitigated the SLE activity by reducing the frequency of activated B cells and plasma cells in MRL\/lpr mice.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> QNZ treatment ameliorated the severity of SLE in MRL\/lpr mice, which may be associated with inhibiting B cell activation, and plasma cell formation. QNZ may be an excellent candidate for the treatment of SLE and other autoimmune diseases.<\/jats:p>","DOI":"10.3389\/fphar.2023.1159075","type":"journal-article","created":{"date-parts":[[2023,5,15]],"date-time":"2023-05-15T13:13:27Z","timestamp":1684156407000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["A quinazoline derivative suppresses B cell hyper-activation and ameliorates the severity of systemic lupus erythematosus in mice"],"prefix":"10.3389","volume":"14","author":[{"given":"Gan","family":"Zhang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuhang","family":"Kong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunfen","family":"Mo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao","family":"Leng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yantang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,5,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/j.neulet.2008.04.091","article-title":"Laminin activates NF-kappaB in Schwann cells to enhance neurite outgrowth","volume":"439","author":"Armstrong","year":"2008","journal-title":"Neurosci. 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