Knockdown of Bcl-3 alleviates psoriasis and dyslipidemia comorbidity by regulating Akt pathway

Allergol Immunopathol (Madr). 2022 Nov 1;50(6):115-121. doi: 10.15586/aei.v50i6.683. eCollection 2022.


Background: Psoriasis is considered as an inflammatory skin disease accompanied by dyslipidemia comorbidity. B-cell leukemia-3 (Bcl-3) belongs to IκB (inhibitor of nuclear factor kappa B [NF-κB]) family, and regulates inflammatory response through associating with NF-κB. The role of Bcl-3 in psoriasis was investigated in this study.

Methods: Apolipoprotein E (ApoE)-deficient mice were treated with imiquimod to induce psoriasis and dyslipidemia. Mice were injected intradermally in the back with lentiviral particles encoding Bcl-3 small hairpin RNA (shRNA). Hematoxylin and eosin were used to detect pathological characteristics. The blood lipid levels were determined by automatic biochemical analyzer, and inflammation was assessed by enzyme-linked-immunosorbent serologic assay and real-time quantitative reverse transcription polymerase chain reaction.

Results: Bcl-3 was elevated in imiquimod-induced ApoE-deficient mice. Injection with lentiviral particles encoding Bcl-3 shRNA reduced Psoriasis area and severity index (PASI) score in ApoE-deficient psoriatic mice. Knockdown of Bcl-3 also ameliorated imiquimod-induced psoriasiform skin lesions in ApoE-deficient mice. Moreover, loss of Bcl-3 enhanced expression of loricrin, an epidermal barrier protein, reduced expression of proliferating cell nuclear antigen (PCNA) and lectin-like oxidized LDL (oxLDL) receptor-1 (LOX-1) in imiquimod-induced ApoE-deficient mice. The enhanced levels of blood lipid in ApoE-deficient mice were attenuated by silencing of Bcl-3 with increase of high-density lipoprotein, and reduction of total cholesterol, triglycerides, and low-density lipoprotein cholesterol. Knockdown of Bcl-3 attenuated imiquimod-induced decrease of transforming growth factor beta (TGF-β), and increase of Interleukin (IL)-17A, IL-23, IL-6, and tumor necrosis factor-α (TNF-α) in ApoE-deficient mice. Protein expression of phospho-Akt (p-Akt) and p-GSK3β in ApoE-deficient psoriatic mice was decreased by silencing of Bcl-3.

Conclusion: Loss of Bcl-3 exerted anti-inflammatory effect on psoriasis and dyslipidemia comorbidity through inactivation of Akt/GSK3β pathway.

Keywords: Akt/GSK3β; ApoE-deficient; Bcl-3; dyslipidemia comorbidity; imiquimod; psoriasis.

MeSH terms

  • Animals
  • Apolipoproteins E / adverse effects
  • Apolipoproteins E / metabolism
  • Cholesterol
  • Comorbidity
  • Disease Models, Animal
  • Dyslipidemias*
  • Glycogen Synthase Kinase 3 beta / metabolism
  • Glycogen Synthase Kinase 3 beta / pharmacology
  • Imiquimod / adverse effects
  • Imiquimod / metabolism
  • Leukemia, B-Cell* / metabolism
  • Leukemia, B-Cell* / pathology
  • Mice
  • Mice, Inbred BALB C
  • NF-kappa B / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Psoriasis* / drug therapy
  • Psoriasis* / metabolism
  • RNA, Small Interfering / adverse effects
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Skin / pathology


  • Imiquimod
  • NF-kappa B
  • Proto-Oncogene Proteins c-akt
  • Glycogen Synthase Kinase 3 beta
  • RNA, Small Interfering
  • Cholesterol
  • Apolipoproteins E