Prospective study on the relationship between CCL22, a cord blood chemokine, and risk of atopic diseases / 临床儿科杂志

Objective To investigate the risk of atopic disease in infants with a atopic mothers. Methods The level of CCL22 and total IgE in the cord blood were measured using ELISA for 33 newborns with atopic mothers and for 44 newborns with non-atopic mothers. Correlation between the two factors was examined. Periodic follow-ups were conducted on the newborns to observe the risk of atopic diseases. Results The atopic group showed a higher level of CCL22 than that in non-atopic group, and the difference was statistically significant (Z=5.20, P=0.000). When 0.9 kU/L was taken as the threshold of an elevated IgE level in cord blood, the positive rates of the atopic group (11/33) was much higher than that of the non-atopic group (4/44) (χ2=7.07, P=0.008). Furthermore, the level of CCL22 and the level of IgE were significantly positively correlated (r=0.808, P=0.000; r=0.348, P=0.021) in the atopic group and the non-atopic group, respectively. During the 12 months of follow-up, the number of atopic diseases occurred in the infants in the atopic group (24/33) was much higher than that in the non-atopic group (10/44) (χ2=19.12, P<0.001).Significant correlation exists between levels CCL22 and total IgE in cord blood and infant atopic diseases (Z=5.36, P=0.000; Z=4.44, P=0.000). Conclusions At birth, the infants with an atopic mother are already in a sensitization state and have a tendency to develop potential atopic diseases. There is a correlation between the history of atopic diseases in the mothers and the elevated level of CCL22 in the cord blood of the newborns, and the probability of developing atopic diseases for the newborns is significantly higher when the level of CCL22 is elevated. The combined detection of CCL22 and IgE levels impact significantly on the prediction of the risk of atopic diseases clinically.

Mechanism of Macrophage-Derived Chemokine/CCL22 Production by HaCaT Keratinocytes

BACKGROUND: CC chemokine ligand 17 (CCL17) and CCL22 are the functional ligands for CCR4. We previously reported that inhibitors of nuclear factor-kappa B and p38 mitogen-activated protein kinase (p38 MAPK), but not of extracellular signal-related kinase (ERK), inhibited tumor necrosis factor (TNF)-alpha- and interferon (IFN)-gamma-induced production of CCL17 by the human keratinocyte cell line, HaCaT. Further, an inhibitor of epidermal growth factor receptor (EGFR) enhanced the CCL17 production by these keratinocytes. OBJECTIVE: To identify the mechanism underlying CCL22 production by HaCaT cells. METHODS: We investigated the signal transduction pathways by which TNF-alpha and IFN-gamma stimulate HaCaT cells to produce CCL22 by adding various inhibitors. RESULTS: TNF-alpha- and IFN-gamma-induced CCL22 production was inhibited by PD98059, PD153035, Bay 11-7085, SB202190, c-Jun N-terminal kinase (JNK) inhibitor II, and Janus kinase (JAK) inhibitor 1. CONCLUSION: Our results indicate that CCL22 production in HaCaT cells is dependent on ERK, EGFR, p38 MAPK, JNK, and JAK and is mediated by different signal pathways from those regulating CCL17 production. Altogether, our previous and present results suggest that EGFR activation represses CCL17 but enhances CCL22 production by these cells.

Therapeutic effects of recombinant Salmonella typhimurium harboring CCL22 miRNA on atopic dermatitis-like skin in mice

Th-2-biased immune responses are known to play a key role in the pathogenesis of atopic dermatitis. In particular, the macrophage-derived chemokine CCL22 is directly implicated in Th-2-associated skin inflammatory reactions, and its levels are significantly elevated in serum and are correlated with disease severity in atopic dermatitis. In this study, we tested the development of genetic therapeutic options to treat atopic dermatitis using bacteria expressing miRNA. We constructed a recombinant strain of Salmonella typhimurium expressing CCL22 miRNA (ST-miRCCL22) for the in vivo knockdown of CCL22. The CCL22 gene was downregulated with CCL22 miRNA in activated lymphocytes. In mice with a cutaneous disease similar to atopic dermatitis, interleukin-4 was inhibited and interferon-gamma was induced after treatments with ST-miRCCL22. Furthermore, CCL22 levels were suppressed in the atopic mice treated with ST-miRCCL22. These results suggest that ST-miRCCL22 may be an effective genetic agent for treating atopic dermatitis.

Roles of the chemokine CCL22 and its receptor CCR4 in the pathogenesis of systemic lupus erythematosus / 中华皮肤科杂志

Objective To investigate the expression of cellular chemokine CCL22 and its receptor CCR4, as well as its clinical significance in systemic lupus erythematosus (SLE), along with its roles in the pathogenesis of this disease. Methods Forty-eight patients with SLE and 26 normal human controls were recruited into this study. The patient cohort included 2 males and 46 females with an average age of 33.98± 12.73 years and disease course of 1 month to 20 years. Blood samples were collected from the subjects. ELISA and flow cytometry were used to examine the plasma concentration of CCL22 together with the CCR4 expression on peripheral blood cells. SLEDAI was applied to evaluate the severity of SLE patients. Results The plasma concentration of CCL22 was 227.03±122.84 ng/L in SLE group, 369.53±79.10 ng/L in the control group, 168.09±61.83 ng/L in patients with lupus nephritis and 292.77±163.45 ng/L in patients without lupus nephritis; there was a significant difference between the SLE patients and normal con-trols (P < 0.05) as well as between patients with lupus nephritis and those without (P < 0.05). Increased percentage of CCR4-expressing cells were observed in the peripheral blood of patients with SLE compared with the controls (20.24%±13.86% vs 10.44%±3.07%, P < 0.01), and the percentage of CD3+CCR4+ cells was significantly higher than that of CD3-CCR4+ cells. Moreover, a decrease was noted in the plasma con-centration of CCL22 in severe patients (P < 0.05). In SLE patients, the percentage of CCR4 increased with the rise in SLEDAI score, whereas the plasma concentration of CCL22 negatively correlated with SLEDAI score (r = -0.308, P < 0.05). Conclusion CCL22/CCR4 may play a certain role in the development, pro-gression and organ involvement in SLE.